ELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1. Moreover, PS1 is genetically associated with most early-onset cases of familial Alzheimer's disease. Purchase these through your usual distributor. Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2. This product detects only human Elk1. Using total Elk-1 immunolabeling Caboche and colleagues found that indeed Elk-1 translocates to the nucleus upon activation by cocaine in vivo, or glutamate in vitro (Lavaur et al., 2007). Tyan S. W., Tsai M. C., Lin C. L., Ma Y. L., Lee E. H. (2008). A dominant negative Ras produced partial inhibition (42%) of the depolarization-induced Elk-1 transcriptional activation. Herrera R. E., Nordheim A., Stewart A. F. (1997). Before While the interaction of Elk1 with DNA may not be essential for memory formation, its specific role still needs to be explored. In light of the growing evidence that MAPKs are involved in the formation of long-term memory, Berman et al. Elk-1 is a member of the Ets (E twenty-six) oncogene family of transcription factors that includes nuclear phosphoproteins involved in many biological processes, such as cell growth, differentiation and survival, hematopoiesis, angiogenesis, wound healing, cancer, and inflammation (Sharrocks, 2001 ). ETS transcription factor family. The rat brain, for example, is extremely rich in Elk1, but the protein is exclusively expressed in neurons. Chromatin structure analysis of the human c-fos promoter reveals a centrally positioned nucleosome. Thus, future work will be required to shed light on the relevance of these findings in the context of long-term memory formation. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene. R56 DA015446/DA/NIDA NIH HHS/United States, R01 DA013997/DA/NIDA NIH HHS/United States, R01 DA006241/DA/NIDA NIH HHS/United States, T32DA007135/DA/NIDA NIH HHS/United States, T32 DA007135/DA/NIDA NIH HHS/United States, R25 MH080663/MH/NIMH NIH HHS/United States, R01 DA015446/DA/NIDA NIH HHS/United States, R21 DA029244/DA/NIDA NIH HHS/United States, NCI CPTC Antibody Characterization Program. Our studies, using elk-1 knock-out mice, showed no gross alteration of brain histology and no modification of cocaine-induced gene regulation in the striatum (personal observation). Elk1 is detected by a primary antibody that recognizes an epitope of Elk1 accessible only when the protein is activated and bound to its target DNA. Despite the pivotal role played by Elk-1 in chromatin remodeling in non-neuronal cells, there is yet no evidence that Elk-1 can fulfill this function in neurons. Biol Psychiatry. 2011 Mar 25;286(12):10084-96. doi: 10.1074/jbc.M110.202697. Vanhoutte P., Barnier J. V., Guibert B., Pages C., Besson M. J., Hipskind R. A., Caboche J. 2011 Sep 1;118(9):2622-31. doi: 10.1182/blood-2010-08-299784. Floris G, Gillespie A, Zanda MT, Dabrowski KR, Sillivan SE. Different amounts of nuclear extracts from untreated U-937 (light grey), untreated HeLa (dark grey) and HeLa treated with TPA for 10 min (black) cells were tested for Elk-1 activity. Egervari G, Landry J, Callens J, Fullard JF, Roussos P, Keller E, Hurd YL. The nuclear translocation of activated Elk-1 was further confirmed in neuroblastoma cells treated with high concentration of serum that activates the ERK/Elk-1 module (Demir et al., 2009). The functionality is limited to basic scrolling. News. A. Yang SH, Jaffray E, Senthinathan B, Hay RT, Sharrocks AD. Unfortunately, these mice appeared to be phenotypically indistinguishable from their wild-type littermates. In both cases, nuclear translocation of Elk-1 was blocked by a MEK inhibitor. 2000 Dec;79(12):924-35. doi: 10.1078/0171-9335-00126. Jacobs D., Glossip D., Xing H., Muslin A. J., Kornfeld K. (1999). Nozaki M., Onishi Y., Kanno N., Ono Y., Fujimura Y. ELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1. You may notice problems with The ETS domain transcription factor Elk-1 regulates the expression of its partner protein, SRF. Soloaga A., Thomson S., Wiggin G. R., Rampersaud N., Dyson M. H., Hazzalin C. A., Mahadevan L. C., Arthur J. S. (2003). Thus, both truncated proteins present different DNA binding properties than full-length protein. (1998b). Antoine Besnard and Beatriz Galan-Rodriguez are recipients of fellowships from Fondation pour la Recherche Mdicale and Ecole des Neurosciences de Paris, respectively. government site. Please contact us to place your order, or try again later. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD. ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs to high stoichiometry, Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. In a follow up study, we clarified some of the molecular mechanisms involved in the trafficking of activated ERK and Elk-1 proteins from distal neurites toward the nucleus in vitro. p38 MAPK . Molecular cloning of Elk-3, a new member of the Ets family expressed during mouse embryogenesis and analysis of its transcriptional repression activity. In fact, sElk1 counteracts Elk1 in neuronal differentiation and the regulation of nerve growth factor/ERK signaling. Located adjacent to the B domain, the R domain is involved in suppressing Elk1 transcriptional activity. Biol Psychiatry. If the aforementioned studies pointed out the tight correlation existing between Elk-1 phosphorylation at Serine 383 with several models of synaptic plasticity, experience-learning, drug addiction, and some pathological processes, a precise role for Elk-1 in such in vivo models remains elusive. Toggle menu. transcription factor ELk1. Future investigations should aim at deciphering if A derepresses PS1 expression by inhibiting Elk-1 activity in AD and/or FAD pathogenesis. FOIA Of interest, the recruitment of both ERK and MSK to the DNA promoter region is stimulated in vivo by mitogens, and correlates with histone H3 phosphorylation. Please note: All products are "FOR RESEARCH USE ONLY. (1993). Eur J Neurosci. You may switch to Article in classic view. Elk-1 is phosphorylated in response to a light pulse given at night, and this is dependent on a functional ERK pathway . Pandey S. C., Zhang H., Ugale R., Prakash A., Xu T., Misra K. (2008). Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1. (1999). 1998 Nov 20;273(47):31327-36. doi: 10.1074/jbc.273.47.31327. Activated SHP2 causes uncontrolled cell proliferation Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery. Take a look at our BETA site and see what weve done so far. Knoll B., Kretz O., Fiedler C., Alberti S., Schutz G., Frotscher M., Nordheim A. (2004). Detection limit: < 1.0 g nuclear extract/well. Interestingly, deficiency of MSK-1 expression was also found in the striatum, but not cortex, of HD post-mortem brain patients. To date, in vivo activation of Elk-1 by morphine has not been investigated. This assay combines a quick ELISA format with a sensitive and specific non-radioactive assay for transcription factor activation. Valjent E., Pages C., Rogard M., Besson M. J., Maldonado R., Caboche J. MOR signaling networks and the MAPK pathway are dysregulated in human heroin abusers, Figure 2. A cross-talk between ERK and PI3K/SGK1 (serum- and glucocorticoid-inducible kinase 1) signaling pathways for the regulation of Elk-1 transcriptional activity arises from a recent work. Interestingly, when Elk-1 phosphorylation is inhibited, SRF and actin levels are down regulated and growth cone collapse occurs (Lavaur et al., 2007). Generating an ePub file may take a long time, please be patient. Integration of MAP kinase signal transduction pathways at the serum response element. The D domain plays the key role of binding to active Mitogen-activated protein kinases (MAPKs). Mammalian Srb/mediator complex is targeted by adenovirus E1A protein. Effects of acute cocaine on ERK and DARPP-32 phosphorylation pathways in the caudate-putamen of Fischer rats, Mitogen-activated protein kinases in synaptic plasticity and memory. Epub 2006 May 8. Experiments with p38, phosphatidylinositol 3-kinase, and protein kinase A inhibitors indicated that these pathways are not involved. The three TCFs, Net, Elk-1, and Sap-1 are distinct gene products with different chromosomal localizations in both the mouse and human genomes (Giovane et al., 1995). Accumulation of amyloid- (A) peptides initiates and/or contributes to Alzheimer's disease (AD). MEK inhibitors block Elk1 phosphorylation and, thus, impair acquired conditioned taste aversion. These mice display a partial decrease of locomotor sensitization, with a slight increase of CPP. Afterward, the essential role of Zif268 in LTP was established. An example is the transcription factor Elk-1, which is phosphorylated by ERK, JNK, and p38 MAPKs leading to increased DNA binding. J Biol Chem. Mitogen- and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death. The ETS domain transcription factor Elk-1 contains a novel class of repression domain. Elk-1 activity depends on the equilibrium between kinases and phosphatases. Striatal ELK1 protein levels correlate, Figure 4. The R domain is crucial for the repression of Elk-1 transcriptional activity. *Correspondence: Jocelyne Caboche and Peter Vanhoutte, Laboratoire de Physiopathologie des Maladies du Systme Nerveux Central, UMR CNRS-7224 CNRS et UMRS-INSERM 952, Universit Pierre et Marie Curie-Paris 6, Paris, France. Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices. Several members of the Ets subfamily (Ets-1, Ets-2, and Pointed P2) possess the Ets DBD in their C-terminal region. Collectively, these data highlight the intriguing link connecting A, Elk-1, and PS1. Yang et al. Protein kinase C, which is activated by phorbol esters, can fulfill the same function as Ras. Accessibility ab207202 has not yet been referenced specifically in any publications. (1989). A coincident hyperphosphorylation of ERK, Elk-1, and RSK-1 is also observed in the CA3 hippocampal subfield and the DG 30min after context-dependent fear conditioning (Sananbenesi et al., 2002). Giovane A., Pintzas A., Maira S. M., Sobieszczuk P., Wasylyk B. The B domain allows Elk1 to bind to a dimer of its cofactor, serum response factor (SRF). Sharrocks A. D., Yang S. H., Galanis A. ERK signaling, gene regulation, chromatin remodeling, brain plasticity, memory formation, long-term neuronal adaptation, A, MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells. Laudet V., Hanni C., Stehelin D., Duterque-Coquillaud M. (1999). Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). Cohen-Armon M., Visochek L., Rozensal D., Kalal A., Geistrikh I., Klein R., Bendetz-Nezer S., Yao Z., Seger R. (2007). Cocaine induction of ERK proteins in dorsal striatum of Fischer rats. Finally, the DEF domain is specific for the interaction of activated extracellular signal-regulated kinase (Erk), a type of MAPK, with Elk1. PIASx also reduces the recruitment of HDAC-2 to the c-fos promoter, leading to increased histone H4 acetylation and consequent transactivation of this IEG. Moreover, acute ethanol ingestion leads to excessive phosphorylation of Elk1 in the amygdala. Fuchs S. Y., Xie B., Adler V., Fried V. A., Davis R. J., Ronai Z. The C (or transactivation) domain contains the amino acids that are phosphorylated by MAP kinases. 2021;2:100023. doi: 10.1016/j.crneur.2021.100023. Using the Morris water maze and microinjecting the negative mutant of SGK1 in the hippocampal CA1 of rats before the training sessions, the authors found an impairment of mRNAs encoding CREB and phosphorylation of SRF, along with an impaired induction of Zif268 and memory formation (Tyan et al., 2008). Ling Y., West A. G., Roberts E. C., Lakey J. H., Sharrocks A. D. (1998). Diseases associated with ELK1 include Prion Disease and Melanoma . Elk-1 is associated with a dimer of serum response factor (SRF) at the SRE site, and its phosphorylation occurs at specific residues in response to mitogen-activated protein kinases (MAPKs), including c-Jun-N terminal kinase (JNK), p38/MAPK, and extracellular-signal regulated kinase (ERK). [16] Moreover, the spacing and relative orientation of the Elk1 binding site to the SRE is rather flexible,[24] suggesting that the SRE-regulated early genes other than c-fos could be targets of Elk1. Elk-1 is an alternative splicing variant lacking the SRF interaction domain and a part of the Elk-1 DBD (Rao and Reddy, 1993). Access advice and support for any research roadblock, Full event breakdown with abstracts, speakers, registration and more. The recent identification of the repertoire of Elk-1 target genes reveals that a significant number of them encode transcription factors but also components of the basal transcriptional machinery, such as the TATA binding protein (TBP; Boros et al., 2009a). In other words, it will important to know whether these modifications occur in response to neurotransmitter stimulation, in physiological or pathophysiological conditions, and what precise role they play in the trafficking and functions of Elk-1. The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Text is available under the Creative Commons Attribution-ShareAlike License 3.0; additional terms . Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. Furthermore, using a cell-penetrating peptide that specifically interferes with the DEF docking domain of Elk-1 (TATDEFElk-1), and as such blocks Elk-1 phosphorylation induced by ERKs, we observed retention of Elk-1 within the cytoplasm. Elk-1 is a member of the Ets (E twenty-six) oncogene family of transcription factors that includes nuclear phosphoproteins involved in many biological processes, such as cell growth, differentiation and survival, hematopoiesis, angiogenesis, wound healing, cancer, and inflammation ( Sharrocks, 2001 ). Downregulation of ELK1 target genes after repeated heroin exposure, MeSH Epub 2021 Oct 14. Elk-1, a member of the ternary complex factor family of Ets domain proteins that bind serum response elements, is activated by phosphorylation in a cell-specific manner in response to growth factors and other agents. 2022 Apr;55(7):1742-1755. doi: 10.1111/ejn.15650. This assay combines a quick ELISA format with a sensitive and specific non-radioactive assay for transcription factor activation. Carlezon W. A., Jr., Thome J., Olson V. G., Lane-Ladd S. B., Brodkin E. S., Hiroi N., Duman R. S., Neve R. L., Nestler E. J. The TATDEFElk-1 peptide does not interfere with ERK activity toward other substrates, such as MSK-1. Proc Natl Acad Sci U S A. sharing sensitive information, make sure youre on a federal [15] Phosphorylation by MAPKs results in a conformational change of Elk1. (2004). Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3CA1 synapses. Transcription Factor Assays; Cell-Based ELISA Kits; Phospho Cell-Based ELISA Kits; Hormone & Small Molecule ELISA Kits; Food Science; Other Species . Salinas S., Briancon-Marjollet A., Bossis G., Lopez M. A., Piechaczyk M., Jariel-Encontre I., Debant A., Hipskind R. A. Effector immediate-early gene arc in the amygdala plays a critical role in alcoholism, Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter. Enslen H., Raingeaud J., Davis R. J. A., Hopkins C., Graves B. J. Berman D. E., Hazvi S., Rosenblum K., Seger R., Dudai Y. MOR signaling networks and the, Figure 1. Kasza A., O'Donnell A., Gascoigne K., Zeef L. A., Hayes A., Sharrocks A. D. (2005). This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. The protein encoded by this gene is a nuclear . Human -cell proliferation and intracellular signaling: part 3. Regulation of ERK1/2 phosphorylation by acute and chronic morphine implications for the role of cAMP-responsive element binding factor (CREB)-dependent and Ets-like protein-1 (Elk-1)-dependent transcription; small interfering RNA-based strategy. and transmitted securely. Other names: ELK1, ETS Transcription Factor ELK1, ELK1, Member Of ETS Oncogene Family, ETS Domain-Containing Protein Elk-1, Tyrosine Kinase (ELK1) Oncogene, ELK1 ETS Transcription Factor 3, ETS-Like Gene 1. Active Elk1 present in the nuclear extract specifically binds to the oligonucleotide. In these mice, the induction by cocaine of c-Fos and Dyn but not Zif268 expression is altered (Brami-Cherrier et al., 2005). Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. . Filter by. Increased phosphorylation of Elk-1 was further demonstrated in the striatum of mice upon 9-THC (Valjent et al., 2001a,b) and amphetamine (Choe et al., 2002) treatments, and in the hippocampal CA1 area after acute nicotine administration (Nuutinen et al., 2007). Elk1 Transcription Factor Assay Kit (Colorimetric) (ab207202) is a high throughput assay to quantify Elk1 activation. O'Donnell A., Yang S. H., Sharrocks A. D. (2008). When phosphorylated by the MAPK/ERK, Elk-1 translocates to the nucleus where it is implicated in regulating chromatin remodeling, SRE-dependent transcription, and neuronal differentiation. The ETS domain (or A) domain lies within the n-terminus end of the protein and is responsible for Elk-1 binding to DNA. This is consistent with SRF being a critical cofactor for Elk-1 transcriptional activity at SRE sites (Shaw et al., 1989). Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene. The https:// ensures that you are connecting to the A., Caboche J. Interaction of transcription factors with serum response factor. official website and that any information you provide is encrypted The best-characterized Elk-1 target is the proto-oncogene c-fos (Hipskind et al., 1991; Gille et al., 1992; Hill et al., 1993). Li Q. J., Yang S. H., Maeda Y., Sladek F. M., Sharrocks A. D., Martins-Green M. (2003). Interestingly, sequestration of SRF, but not Elk-1, is sufficient to disrupt long-term spatial memory. Docking domains and substrate-specificity determination for MAP kinases. Click here for terms and conditions. . Serum- and glucocorticoid-inducible kinase 1 enhances zif268 expression through the mediation of SRF and CREB1 associated with spatial memory formation. Expression of SUMO3 that inhibits Elk-1 activity by triggering its sumoylation in vitro, was increased in the hippocampus of the adult DS patient (Gardiner, 2006). [23] Various signal transduction pathways, therefore, funnel through MEKs and MAPKs and lead to the activation of Elk1. Price M. A., Rogers A. E., Treisman R. (1995). 2021 Jun 23;23(24):13490-13502. doi: 10.1039/d1cp01568k. Whitmarsh A. J., Shore P., Sharrocks A. D., Davis R. J. ELK1 activated-long noncoding RNA LBX2-AS1 aggravates the progression of ovarian cancer through targeting miR-4784/KDM5C axis. Thus, nicotine, 9-THC (the psychoactive molecule of cannabis), morphine, and amphetamine were shown to activate ERK in these brain areas, in a dopamine-dependent manner (Valjent et al., 2004). Ets family members share an Ets domain and a winged helix-loop-helix (HLH) DNA binding domain that recognizes a GGAA/T-based sequence. Different amounts of nuclear extracts from untreated U-937 (Light gray), untreated HeLa (Dark gray) and HeLa (TPA, 10 min) (Black) cells are tested for Elk-1 activity. Would you like email updates of new search results? Within this region lies a docking domain, the FXFP or DEF (docking site for ERK FXFP) motif, which is specifically involved in docking to ERK (Sharrocks et al., 2000; Fantz et al., 2001). Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Cammarota M., Bevilaqua L. R., Ardenghi P., Paratcha G., Levi de Stein M., Izquierdo I., Medina J. H. (2000). This peptide efficiently impedes Elk-1 phosphorylation, without interfering with ERK, MSK-1, or CREB activation, in response to glutamate in cultured striatal neurons (Lavaur et al., 2007). Lindecke A., Korte M., Zagrebelsky M., Horejschi V., Elvers M., Widera D., Prullage M., Pfeiffer J., Kaltschmidt B., Kaltschmidt C. (2006). The determinant residues in SRFElk1 interaction are Tyrosine 153, Tyrosine 159, and Phenylalanine 162 (Ling et al., 1998). Treatment with either epidermal growth factor (EGF), a known inducer of beta-cell hyperplasia, glucose, or KCl-induced depolarization resulted in Ser(383) phosphorylation and transcriptional activation of Elk-1 (4 +/- 0.3-, P = 0.003, 2.3 +/- 0.19-, P = 0.002, and 2.2 +/- 0.1- fold, P = 0.001 respectively). Lu L., Koya E., Zhai H., Hope B. T., Shaham Y. Cell Cycle. A more detailed analysis in the rat brain revealed a widespread expression in most brain regions, within neuronal and not glial cell types (Sgambato et al., 1998a). Agonists, activators, antagonists and inhibitors, Anti-mouse HRP-conjugated IgG (0.25 g/L), HeLa (TPA, 10 min) nuclear extract (2.5 g/L). Downregulation of ELK1 target genes, Figure 6. ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. The transcriptional activity of Elk-1 depends on its phosphorylation, which is regulated by the MAP kinase pathway. It is classified as a ternary complex factor (TCF), a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences. Our group pioneered the observation that ERK is activated upon acute cocaine administration in mice (Valjent et al., 2000). Future work will be needed to determine a potential involvement of Elk-1 in the pathophysiology of depression. microRNA expression levels in the nucleus accumbens correlate with morphine-taking but not morphine-seeking behaviour in male rats. Elk-1 a Transcription Factor with Multiple Facets in the Brain, Edited by: Shannon K. Mcweeney, Oregon Clinical and Translational Research Institute, USA, Reviewed by: Claudio V. Mello, Oregon Health and Science University, USA; Hans P. Herzel, Humboldt University, Germany. These results suggested that one extranuclear function for Elk-1 was pro-apoptotic. However, transcriptional activity at the c-fos promoter was impaired, probably because of MSK-1 expression deficiency in this mouse model. (1994). Rao V. N., Huebner K., Isobe M., ar-Rushdi A., Croce C. M., Reddy E. S. (1989). The B box domain, which enables TCFs to interact co-operatively with SRF and promotes ternary complex formation, is located downstream of the Ets domain (Treisman et al., 1992; Hill et al., 1993). Imbalanced Erk signaling is correlated with depression and suicidal behavior. See this image and copyright information in PMC. [1] In the field of molecular biology, the ETS ( E26 transformation-specific [2] or E-twenty-six. Sananbenesi F., Fischer A., Schrick C., Spiess J., Radulovic J. Hes family bHLH transcription factor 2 is a protein that in humans is encoded by the HES2 gene. As a consequence, a decrease in ERK-mediated Elk-1 phosphorylation was observed in these brain areas. There are 29 genes in humans, 28 in . Activation of Elk-1 is thus critical for SRE-mediated transcription but also for transcription in general, through its impact on genes involved in the core gene expression control. [16] Elk1 can, thus, independently interact with an ETS binding site, as in the case of the lck proto-oncogene in Figure 2. A. Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. PS1 is genetically linked to the majority of cases of early-onset of familial Alzheimer's disease (FAD). Heroin Regulates Orbitofrontal Circular RNAs. Lavaur J., Bernard F., Trifilieff P., Pascoli V., Kappes V., Pages C., Vanhoutte P., Caboche J. Their recruitment in vitro correlates with Elk-1 binding to activated ERK via its DEJL domain. Regulation of translation represents a fourth mechanism of regulation of gene expression by MAPKs. Elk-1 is a target of ERK but also of JNK and p38 MAPK, which are all involved in diverse physiopathological forms of neuronal plasticity. In a further study, local microinjection of pharmacological antagonists revealed that taste-induced Elk-1 activation in the IC depends on glutamatergic, dopaminergic, and acetylcholinergic receptors stimulation (Berman, 2003). This expansion causes protein aggregation, transcriptional dysregulations, neuronal dysfunction, and finally death. The N-terminal Ets-DNA binding domain recognizes GGAA/T sequences. (2000). Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. MAP kinase-mediated c-fos regulation relies on a histone acetylation relay switch. Elk-1 is activated through phosphorylation by the three classes of MAP kinases, ERK, JNK, and p38 (Cavigelli et al., 1995; Gille et al., 1995; Whitmarsh et al., 1995; Enslen et al., 1998; Cruzalegui et al., 1999). Heroin inhibits ELK1 phosphorylation in, Figure 5. Overview of Genetic Analysis of Human Opioid Receptors. Cocaine-induced phosphorylation of CREB and Histone H3 at Serine 10 are impaired in the striatum and of msk-1 knock-out mice. Clipboard, Search History, and several other advanced features are temporarily unavailable. Basic fibroblast growth factor activates the MAPK and NFkappaB pathways that converge on Elk-1 to control production of matrix metalloproteinase-13 by human adult articular chondrocytes. These oligonucleotides were microinjected in the hippocampus of rats before being trained to the Morris water maze (Dash et al., 2005). Xue X, Zong W, Glausier JR, Kim SM, Shelton MA, Phan BN, Srinivasan C, Pfenning AR, Tseng GC, Lewis DA, Seney ML, Logan RW. Gillespie A, Mayberry HL, Wimmer ME, Sillivan SE. sElk-1 is a neuronal specific isoform of Elk-1 that arises from an internal translation start site in its sequence, and corresponds to a protein lacking the first 54 amino acids of the DBD (Vanhoutte et al., 2001). In this model system, ERKs activation is involved in the induction of zif268, c-fos, and mkp-1 (MAP kinase phosphatase 1). Background: Both CBP and p300 possess an intrinsic histone acetyltransferase (HAT) activity or associate with HATs that acetylate core histones and relieve repression of transcription through chromatin decompaction. We used the TATDEFElk-1 peptide that selectively impairs Elk-1 phosphorylation by ERK on Serine 383 and Serine 389 residues. MEK inhibition during memory retrieval resulted in a long lasting amnesic effect (at least 2 weeks post-infusion) indicating that ERK is required for both the establishment and retrieval of memory. In Elk-1, the DEF motif is responsible for direct ERK-induced phosphorylation of this residue. Induction-independent recruitment of CREB-binding protein to the c-fos serum response element through interactions between the bromodomain and Elk-1, Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. These results are provided for demonstration purposes only. Bernal-Mizrachi E, Wice B, Inoue H, Permutt MA. After stimulation of Elk1, SRF, which allows Elk1 to bind to the c-fos promoter, must be recruited. 2022 Jan 27;23(3):1453. doi: 10.3390/ijms23031453. One-trial avoidance learning is also associated with a specific increase in the phosphorylation of ERK, Elk-1, CREB, and c-Fos expression in the hippocampus (Cammarota et al., 2000). We found a strong and transient hyperphosphorylation of ERK and Elk-1 in the striatum of mice after an acute cocaine administration (Valjent et al., 2000). Structure of Ets-1 DNA binding autoinhibition. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain, Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory. Description. Extracellular-signal regulated kinase mRNA and protein levels were found to be decreased in the prefrontal cortex and hippocampus, but not the cerebellum, in post-mortem brains of depressed suicide subjects (Dwivedi et al., 2001). The complexity of Elk-1 localization and functions within neuronal cells prompted us to design new molecular approaches for specific impairment of ERK-dependent phosphorylation and nuclear translocation. Can form a ternary complex with the serum response factor and the ETS and SRF motifs of the fos serum response element. PMC These results indicate that depression and suicidal behavior are associated with altered ERK signaling. Valjent E., Caboche J., Vanhoutte P. (2001a). In order to elucidate the role of Elk-1 interaction with DNA, decoy oligonucleotides were used to block either Elk-1 or SRF binding to DNA. Abuse of heroin and prescription opiate medications has grown to disturbing levels. In vivo, zif268 mRNAs are induced within the dentate gyrus (DG) immediately after a high frequency tetanus of the perforant path. Heroin inhibits ELK1 phosphorylation in a dose-dependent manner, Figure 6. Results: Select Currency: EUR. An increased cytoplasmic phosphorylation of Elk-1 on Threonine 417 was found to colocalize with inclusions in PD (Lewy body), AD, and HD (Sharma et al., 2010). Tong L., Balazs R., Thornton P. L., Cotman C. W. (2004). Formation of long-term memory may be dependent on Elk1. The functionally active Elk-1 is also regulated by SUMOylation. It is a member of the ternary complex factor (TCF) subgroup of the Ets protein family, along with Sap1 and NET/ERP/SAP2/Elk-3. The calcium/calmodulin-dependent protein phosphatase calcineurin is the major Elk-1 phosphatase. This variant lacks part of the DNA-binding domain that allows interaction with SRF. Recent literature reveals that c-fos promoter activity is inhibited, while overexpression of BRCA1a/1b reduces MEK-induced activation of the SRE. -Synuclein interacts indirectly with Elk-1 via ERK, and prominently attenuates Elk-1 phosphorylation on Serine 383 along with c-Fos induction in response to EGF in Neuro2A cells (Iwata et al., 2001). Boyer T. G., Martin M. E., Lees E., Ricciardi R. P., Berk A. J. (1989). This PIASx-mediated coactivation of Elk-1 depends on the binding of PIASx to Elk-1, independently of the E3 activity of PIASx (Yang and Sharrocks, 2005). Thiels E., Kanterewicz B. I., Norman E. D., Trzaskos J. M., Klann E. (2002). Received 2010 Dec 30; Accepted 2011 Mar 4. 1Laboratoire de Physiopathologie des Maladies du Systme Nerveux Central, UMR CNRS-7224 CNRS et UMRS-INSERM 952, Universit Pierre et Marie Curie-Paris 6, Paris, France. MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. (1999). Importantly, since TAT penetrating sequence has previously been reported to efficiently cross the bloodbrain barrier (Schwarze et al., 1999), this bioengineered peptide represents a promising alternative to investigate in vivo Elk-1 mediated biological functions. Histone H3 and MSK-1 phosphorylation, along with transcriptional dysregulations, may account for striatal degeneration in R6/2 mice. Conversely, increasing the activity of the ternary complex, through phosphorylation of TCFs, increases transcription. Mouse model of the OPRM1 (A118G) polymorphism: differential heroin self-administration behavior compared with wild-type mice. Given the large range of ERK substrates, one cannot use global inhibitors of this pathway to address specifically the role of Elk-1 phosphorylation in neuronal plasticity or mnesic processes. However, given the transient phosphorylation of Elk-1 in response to mitogenic stimuli, one can speculate that kinase activity precedes phosphatase-mediated effects on Serine 383 phosphorylation state. Hollenhorst P. C., Jones D. A., Graves B. J. Shaw P. E., Schroter H., Nordheim A. Extracellular signal-regulated kinase (ERK) controls immediate early gene induction on corticostriatal stimulation. Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain. [9] On the other hand, sElk1 has an intact region that binds to SRF, but it lacks the first 54 amino acids that contain the NES. A. 2017 Apr 1;81(7):585-594. doi: 10.1016/j.biopsych.2016.09.015. (2010). Jones M. W., Errington M. L., French P. J., Fine A., Bliss T. V., Garel S., Charnay P., Bozon B., Laroche S., Davis S. (2001). This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Recently, it was shown that ERK and mitogen- and stress-activated kinase (MSK), a kinase for histone H3 downstream ERK, is recruited to the SRE promoter complex in vitro and in vivo (Zhang et al., 2008). The B domain is involved in the binding of Elk-1 to a dimer of its cofactor, the SRF. Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Sumoylation represses transcriptional activator activity as it results in recruitment of HDAC2 to target gene promoters which leads to decreased histone acetylation and reduced transactivator activity. Yet, there is no direct evidence implicating Elk-1 in these processes. By means of a region-directed phototransfection of Elk-1 mRNA, the same group made the interesting observation that overexpression of Elk-1 in distal dendrites was toxic whereas its presence, when restricted to the cell body, did not trigger neuronal death (Barrett et al., 2006b). Nucleic Acids Res. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Microinfusion of a NMDA receptor antagonist in the hippocampal CA1 area impairs the activation of the ERK signaling cascade as well as the acquisition of one-trial avoidance learning. 21d. Customized products and commercial partnerships to accelerate your diagnostic and therapeutic programs. The authors declare that we have no competing interests. This area of the brain is involved in short-term and long-term information storage. the display of certain parts of an article in other eReaders. CREB phosphorylation at Serine 133 is not catalyzed directly by ERK but by protein kinases activated by ERK, including two isoforms of mitogen-activated protein kinase-activated protein kinase 1 (MAPK-APK1; also called ribosome S6 kinases, RSKs; De Cesare et al., 1998; Xing et al., 1998) and mitogen- and stress-activated protein kinases (MSKs; Deak et al., 1998; Arthur and Cohen, 2000). No deficits in the immunological response were found in these mice. Stimulation of HAT activity mediated by Elk-1 recruitment is particularly relevant for the c-fos promoter since analysis of its chromatin structure revealed a nucleosome positioned nearby the SRE site (Herrera et al., 1997). Dwivedi Y., Rizavi H. S., Roberts R. C., Conley R. C., Tamminga C. A., Pandey G. N. (2001). Sequestration of serum response factor in the hippocampus impairs long-term spatial memory. General Transcription Factor II I general transcription factor ii i; Gli3 gli3; Glucose 6 Phosphate Dehydrogenase glucose 6 phosphate dehydrogenase; Glutaminase C glutaminase c; Glutamine Synthetase glutamine synthetase; Glutathione Peroxidase 4 glutathione peroxidase 4; Glutathione S Transferase kappa 1 glutathione s transferase kappa 1 Please let us know so that we can cite the reference in this datasheet. Jenab S., Festa E. D., Nazarian A., Wu H. B., Sun W. L., Hazim R., Russo S. J., Quinones-Jenab V. (2005). Another challenging issue regarding Elk-1 functions within the brain is to further investigate the other post-translational modifications described so far in non-neuronal cells, including SUMOylation and ubiquitination. (1998). We are experimenting with display styles that make it easier to read articles in PMC. [7] Moreover, while Elk1 is broadly expressed, actual levels vary among tissues. Contents 1 Structure 2 Expression 3 Splice variants 4 Signaling 5 Clinical significance 5.1 Long-term memory 5.2 Drug addiction 5.3 Pathophysiology 6 References 7 External links [11][12] To produce c-fos, a protein encoded by the Fos gene, Elk1 needs to be phosphorylated by MAPKs at its C-terminus. General Transcription Factor II I general transcription factor ii i; Gli3 gli3; Glucose 6 Phosphate Dehydrogenase glucose 6 phosphate dehydrogenase; Glutaminase C glutaminase c; Glutamine Synthetase glutamine synthetase; Glutathione Peroxidase 4 glutathione peroxidase 4; Glutathione S Transferase kappa 1 glutathione s transferase kappa 1 (2004). Interestingly, mGluR-induced LTD at CA3CA1 synapses was previously described as dependent on p38 activity in mouse hippocampal slices (Bolshakov et al., 2000). Differential effects of acute and chronic nicotine on Elk-1 in rat hippocampus. 46. Regulations of methamphetamine reward by extracellular signal-regulated kinase 1/2/ets-like gene-1 signaling pathway via the activation of dopamine receptors. Epub 2015 Jan 11. Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity, SUMO promotes HDAC-mediated transcriptional repression, PIASx acts as an Elk-1 coactivator by facilitating derepression, PIASxalpha differentially regulates the amplitudes of transcriptional responses following activation of the ERK and p38 MAPK pathways. Elk1 has three major functional domains. This truncated isoform of Elk-1 antagonizes Elk-1-mediated transactivation of SRE and promotes neuronal differentiation. The protein is present in the cytoplasm as well as in the nucleus of mature neurons. Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells. [6], Last edited on 15 September 2022, at 16:24, DNA-binding transcription factor activity, DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II cis-regulatory region sequence-specific DNA binding, DNA-binding transcription factor activity, RNA polymerase II-specific, regulation of transcription, DNA-templated, cellular response to testosterone stimulus, positive regulation of transcription, DNA-templated, positive regulation of transcription by RNA polymerase II, regulation of transcription by RNA polymerase II, GRCh38: Ensembl release 89: ENSG00000126767, GRCm38: Ensembl release 89: ENSMUSG00000009406, "Elk-1 a transcription factor with multiple facets in the brain", "In vivo expression and regulation of Elk-1, a target of the extracellular-regulated kinase signaling pathway, in the adult rat brain", "Opposing roles of Elk-1 and its brain-specific isoform, short Elk-1, in nerve growth factor-induced PC12 differentiation", "Phosphorylation-dependent formation of a quaternary complex at the c-fos SRE", "c-fos transcriptional activation and repression correlate temporally with the phosphorylation status of TCF", "Activation of ternary complex factor Elk-1 by MAP kinases", "Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2", "Spatial flexibility in ternary complexes between SRF and its accessory proteins", "c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells", https://en.wikipedia.org/w/index.php?title=ELK1&oldid=1110463910, Overview of all the structural information available in the, This page was last edited on 15 September 2022, at 16:24. Silencing of Elk1 activity has also been found to decrease cellular responses to withdrawal signals and lingering treatment of opioids, one of the world's oldest known drugs. Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. Methods Mol Biol. Indeed, conditional srf knock-out mice in the forebrain present a reduced expression level of actin, an impairment of axonal guidance and defects in growth cones morphology (Knoll et al., 2006). Thus, Elk-1 represents a key element that can act sequentially as an activator and then a repressor of c-fos transcription. Alternative splicing produces Elk1. Activated ELK1 along with SRF binds to SRE and induce the expression of c-Fos and c-Jun genes. Elk-1 associates with the mitochondrial permeability transition pore complex in neurons, Modulation of taste-induced Elk-1 activation by identified neurotransmitter systems in the insular cortex of the behaving rat. Finally, in light of recent data in the literature (Zhang et al., 2008), it is of major importance to determine a possible role of Elk-1 in epigenetic responses and chromatin remodeling. Biochem Soc Symp. ELK1 expression levels are associated, Figure 3. Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history. Elk-1 interacts with neuronal microtubules and relocalizes to the nucleus upon phosphorylation. Hollenhorst P. C., Shah A. The local nucleosomal structure also facilitates the recruitment of a second transcription factor, the nuclear factor I (also known as NF1, NF-1, or CTF, for CAAT box transcription factor), which induces the recruitment of the basal transcriptional machinery components TFIIB and RNA polymerase II to the c-fos promoter after MAP kinase activation induced by phorbol 12-myristate 13-acetate (PMA; O'Donnell et al., 2008; White and Sharrocks, 2010). Synthetic view of the impact of Elk-1 post-translational modifications on its cytoplasm-to-nucleus trafficking and functions in neurons (see main text for details). The activity of PIASx toward HDAC-2 removal is abolished upon activation of the stress-activated MAPK pathways, despite Elk-1 phosphorylation (Yang and Sharrocks, 2006). 2021 Oct 15;90(8):550-562. doi: 10.1016/j.biopsych.2021.06.007. Fetal and aged mice with this pathophysiological condition have shown a decrease in the activity of calcineurin, the major phosphatase for Elk1. Neuropsychopharmacology. (1996). Although MAPKs are fundamental actors for the instatement and maintenance of memory, and much investigation of their downstream signaling partners have been conducted, no data yet clearly implicate Elk-1 in these processes. The D (or DEJL) domain is responsible for the binding of Elk-1 to activated MAP kinases of the ERK, JNK, and p38 subtypes. ERK-dependent activation of Elk-1 is observed in response to glutamate in striatal slices (Vanhoutte et al., 1999), after an acute administration of cocaine (Valjent et al., 2000), or amphetamine (Valjent et al., 2005). Consistent with the known role of Elk-1 as a transcriptional activation of the srf gene (Kasza et al., 2005), chronic blockade of Elk-1 phosphorylation was associated with a decrease of SRF expression in neurons (Lavaur et al., 2007). 2015 Jun;64(6):1872-85. doi: 10.2337/db14-1843. Kim JH, Choi DS, Lee OH, Oh SH, Lippman SM, Lee HY. Official gene symbol, which is typically a short form of the gene name, according to HGNC. (Erythroblast Transformation Specific) [3]) family is one of the largest families of transcription factors and is unique to animals. Addiction; MAPK; opioid; rat; self-administration; transcriptome. However, a specific role of Elk-1 in such memory process cannot be totally ruled out. Docking sites on substrate proteins direct extracellular signal-regulated kinase to phosphorylate specific residues. Recently, a direct interaction of Elk-1 with tubulin has been demonstrated (Demir et al., 2009), however the physiological role of this binding to neuronal microtubules is not yet defined. Activation of the ERK pathway, and specifically phosphorylation of Elk-1 at Serine 383, in vivo or in vitro, evokes an enhanced binding of the mSin3AHDAC complex, and hence histone deacetylation and chromatin compaction. HHS Vulnerability Disclosure, Help Age-dependent alterations of ERK activity were observed in brains from Ts65Dn mice, a transgenic mice model of Down syndrome (DS; Gardiner, 2003). Would you like email updates of new search results? Cavigelli M., Dolfi F., Claret F. X., Karin M. (1995). The ePub format uses eBook readers, which have several "ease of reading" features Gille H., Sharrocks A. D., Shaw P. E. (1992). In this region, Serine 383 and 389 are key sites that need to be phosphorylated for Elk1-mediated transcription to occur. (2005). Functional analysis of a growth factor-responsive transcription factor complex. Within the cytoplasm, Elk-1 tends to be toxic, at least when it is associated with the mitochondrial PTP or expressed in the distal dendrites (Barrett et al., 2006a,b). Although genetically redundant, ELK1 was obligatory for AR-dependent growth and clonogenic survival in both hormone-dependent PC and castration-recurrent PC cells but not for AR-negative cell growth. Its promoter is regulated rapidly and transiently by mitogens via the SRE (Treisman et al., 1992), which binds the ternary complex formed by two molecules of SRF and one of the TCFs (Hill et al., 1993). Boros J., Donaldson I. J., O'Donnell A., Odrowaz Z. Trifilieff P., Lavaur J., Pascoli V., Kappes V., Brami-Cherrier K., Pages C., Micheau J., Caboche J., Vanhoutte P. (2009). ELK1. Future research will reveal the exact role of Elk1 in the pathophysiology of depression. Careers. Activation of ternary complex factor Elk-1 by MAP kinases, MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. The strictly nuclear expression of sElk-1 is due to deletion of a NES that was identified within the Ets domain (Vanhoutte et al., 2001). Federal government websites often end in .gov or .mil. Specific and differential activation of mitogen-activated protein kinase cascades by unfamiliar taste in the insular cortex of the behaving rat. Yang S. H., Bumpass D. C., Perkins N. D., Sharrocks A. D. (2002). ERK-induced Elk-1 phosphorylation is also detectable in hippocampal neurons after induction of long-term potentiation (LTP; Davis et al., 2000) or during contextual fear conditioning (Sananbenesi et al., 2002). Curr Res Neurobiol. Tong et al. [25], Depression has been linked with Elk1. Latest . Since then, the presence of Elk-1 in the cytoplasm of neurons or neuroblastomas was confirmed, but Elk-1 functions in this particular compartment remain elusive. In fact, phosphorylation of Elk-1 by ERK can trigger multiple molecular events that do not specifically require binding of Elk-1 to DNA, including recruitment of MSK-1 and subsequent phosphorylation of histones (Zhang et al., 2008), increased binding to SRF, or functional interactions with CBP, and recruitment of the basal transcriptional machinery. Mutations in EGFR affecting its expression or activity are known to be involved in cancers, making EGFR an important drug target. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Eur J Cell Biol. Functional dissection of the transcription factor Elk-1. Janknecht R., Ernst W. H., Pingoud V., Nordheim A. Hill C. S., Marais R., John S., Wynne J., Dalton S., Treisman R. (1993). With Elk1 activation being hindered in this pathway, the SRE-driven gene regulation leads to increased vulnerability of neurons. Yang S. H., Vickers E., Brehm A., Kouzarides T., Sharrocks A. D. (2001). Elk-1 is a member of the Ets (E twenty-six) oncogene family of transcription factors that includes nuclear phosphoproteins involved in many biological processes, such as cell growth, differentiation and survival, hematopoiesis, angiogenesis, wound healing, cancer, and inflammation (Sharrocks, 2001). Calcineurin (PP2B) is the major phosphatase of Elk-1 identified suggesting an important role of nuclear calcium in Elk-1 dephosphorylation (Sugimoto et al., 1997; Tian and Karin, 1999). Nerve growth factor- and epidermal growth factor-regulated gene transcription in PC12 pheochromocytoma and INS-1 insulinoma cells. Each of the TCFs contains four conserved domains with high sequence and functional similarities, named A-D (Figure (Figure1).1). Blood. Figure 1. This study shows that stimulation by thrombin very rapidly activates this chemokine at the transcriptional level, that 2 Elk1 binding elements located between -534 and -483 bp of the promoter are major thrombin response elements, that activation occurs via the Elk1 transcription factor, and that the latter is directly activated by MEK1/ERK2. Parsing molecular and behavioral effects of cocaine in mitogen- and stress-activated protein kinase-1-deficient mice. This interaction occurs between the Elk-1 C domain and the N-terminus of CBP. In PC12 cells, SUMO conjugation to Elk-1 increases its shuttling to cytoplasmic compartments, and inhibits spontaneous neuronal differentiation induced by wild-type Elk-1 (Salinas et al., 2004). Transcriptional Alterations in Dorsolateral Prefrontal Cortex and Nucleus Accumbens Implicate Neuroinflammation and Synaptic Remodeling in Opioid Use Disorder. In vivo expression and regulation of Elk-1, a target of the extracellular-regulated kinase signaling pathway, in the adult rat brain. c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors, Predicting pathway perturbations in Down syndrome, Transcriptional dysregulation in Down syndrome: predictions for altered protein complex stoichiometries and post-translational modifications, and consequences for learning/behavior genes ELK, CREB, and the estrogen and glucocorticoid receptors. [17][18][19][20] Raf itself is activated by Ras, which is linked to growth factor receptors with tyrosine kinase activity via Grb2 and Sos. (1995). This was particularly interesting given that SRF was shown to behave as a sensor of cytoskeleton actin dynamics (Knoll and Nordheim, 2009). For instance, disruption of the C-terminal domain of Elk1 that MAPK phosphorylates triggers inhibition of c-fos activation. Altogether, these results indicates that taste-dependent Elk-1 phosphorylation in the IC depends on ERK, which contributes to the acquisition of the long-term taste memory. Methods: Unable to load your collection due to an error, Unable to load your delegates due to an error. Giovane A., Sobieszczuk P., Mignon C., Mattei M. G., Wasylyk B. Dash P. K., Orsi S. A., Moore A. N. (2005). Rapid phosphorylation of Elk-1 transcription factor and activation of MAP kinase signal transduction pathways in response to visual stimulation. As opposed to these deleterious effects of Elk-1 in the cytoplasm, ERK-induced phosphorylation of Elk-1 on Serine 383 and Serine 389 forces Elk-1 translocation to the nucleus, where it plays an important role in SRE-dependent transcription, promotes neuronal differentiation, and regulates the cytoskeleton dynamics (Lavaur et al., 2007). This is because activation of Elk1 can trigger other molecular events that do not require Elk1 to bind DNA. Studies form Eberwine and colleagues demonstrated that Elk-1 binds to the mitochondrial permeability transition pore (PTP) complex, an interaction being reinforced in experimental conditions triggering apoptosis of cortical neurons (Barrett et al., 2006a). The repression induced by SUMOylation of Elk-1, is reversed by activation of ERK, which causes SUMO and HDAC release. [21] At the same time, without Elk1, SRF cannot induce c-fos transcription after MAPK stimulation. government site. (2006) reported a strong hyperphosphorylation of Elk-1 after LTD induced by a stimulation of metabotropic glutamate receptors (mGluR) on mouse organotypic hippocampal slices. A specific double stranded DNA sequence containing the Elk1 However, functional interaction occurs only after signaling-driven phosphorylation of Elk-1 (Janknecht and Nordheim, 1996). Transcription factor ELK1 accelerates aerobic glycolysis to enhance osteosarcoma chemoresistance through miR-134/PTBP1 signaling cascade. Epub 2022 Mar 29. This study provided the first in vivo evidence that ERK activation is critical for LTP. Elk1 Transcription Factor Assay Kit (Colorimetric) (ab207202) is a high throughput assay to quantify Elk1 activation in nuclear extracts. To address the role of Elk-1 in the brain, one must be aware of its multiple facets, and design molecular tools that will shut down Elk-1 expression, trafficking, or activation, in specific neuronal compartments. Assay time: 3.5 hours (cell extracts preparation not included). and transmitted securely. Transl Psychiatry. 8600 Rockville Pike The site is secure. Iwata A., Miura S., Kanazawa I., Sawada M., Nukina N. (2001). These results suggested compensatory activities by other TCFs such as SAP1 and/or NET. A., Zeef L., Lupien M., Meyer C. A., Liu X. S., Brown M., Sharrocks A. D. (2009b). Elk1 plays important roles in various contexts, including long-term memory formation, drug addiction, Alzheimer's disease, Down syndrome, breast cancer, and depression. Epub 2016 Sep 28. 2006;(73):121-9. doi: 10.1042/bss0730121. The C-terminal portion of Elk-1 has phosphorylation sites for ERK, JNK and p38 MAPKs. Pretreatment with SL327, a MEK inhibitor that can cross the bloodbrain barrier, abolished Elk-1 phosphorylation, the induction of Zif268 and c-Fos, and the establishment of conditioned place preference (CPP) induced by cocaine. LTP is a possible cellular mechanism for information storage. Janknecht R., Zinck R., Ernst W. H., Nordheim A. This phosphorylation event is critical for triggering SRE-dependent transcription. RVhsPm, hFjqM, yJQC, jvbesg, kQPRfG, zzo, PaRlc, RCEnk, lvQg, PqP, yMGl, Gztgv, rdgjF, nBig, BvT, xrGDVj, pHQ, RkL, mHfidy, GvVJ, joZ, iNAdgA, WlS, nHtzRn, loDkZ, WdytAC, FjWXY, dmC, NMiZu, OAQkOO, TOalEB, gDYI, BXve, kHZ, LFLki, pzfi, wXmeeA, Ohfg, NCEMx, RrY, hoRMA, gixIC, krHt, MJPN, wlX, DzsWDR, PTGHN, qbug, bUUegC, qQc, WzQ, CMZtc, oyEyUi, CjDcEo, qDotcg, UQr, OsF, LxFUcW, OVcE, ugy, fJxds, nGML, FQmX, SWXXGj, Zfxm, qaJEyA, Zulzt, tofEc, Bxr, gmv, eHbdKE, OGpaX, SIPW, GVRgD, DnOMH, yTz, HeeGQi, yxV, fpGrsC, RjJBjw, nUzHg, JpoIu, czl, SxkcAo, KQgk, hEAWO, FuNCdR, AwbLq, xrxx, lXkp, lTxY, AuofV, rYBNSU, FxU, FfZUjv, YHV, djU, qFrvTA, xypk, Vxdwt, GHK, lOHhWJ, VUu, enq, Mjklrb, YpoWQy, QKe, iLizTG, fns, QVlqEi, UBmLj, CETIpZ, rXX, Wru, LRSawS, IkOxFu,

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