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Gene Review

ELK1  -  ELK1, member of ETS oncogene family

Homo sapiens

Synonyms: ETS domain-containing protein Elk-1
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Disease relevance of ELK1

  • In this study, the ACE66 element is shown to be activated in JEG-3 choriocarcinoma cells through synergistic interactions between consensus DNA motifs for binding of vitamin D receptor, AP1 and ELK1 [1].
  • About 30% of the mutations causing nonsyndromic X-linked mental retardation (MRX) are thought to be located in Xp11 and in the pericentromeric region, with a particular clustering of gene defects in a 7.4 Mb interval flanked by the genes ELK1 and ALAS2 [2].
  • Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types [3].
  • Among the three reported mutations (K438Q, K438T, and T439P) found in non-small cell lung carcinoma and melanoma, none elevated the activity of the MEK/Erk cascade as determined by in vitro kinase assays, immunoblots using antibody specific for phosphorylated Erk, or Elk1-dependent reporter assays [4].
  • A high throughput system for the evaluation of protein kinase C inhibitors based on Elk1 transcriptional activation in human astrocytoma cells [5].

High impact information on ELK1

  • DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation [6].
  • In cortical neurons treated with nerve growth factors and in stimulated cardiomyocytes, PARP-1 activation enhanced ERK-induced Elk1-phosphorylation, core histone acetylation, and transcription of the Elk1-target gene c-fos [6].
  • Immunoblotting and EMSA revealed that transfection of CagA enhanced phosphorylation of and DNA binding by Elk1 [7].
  • Since MAPK has been shown to phosphorylate and activate nuclear targets, such as the transcription factor Elk1, it has been proposed, but not yet demonstrated, that MAPK nuclear translocation could represent a critical step in signal transduction [8].
  • In contrast, prevention of MAPK nuclear translocation strongly inhibited Elk1-dependent gene transcription and the ability of cells to reinitiate DNA replication in response to growth factors [8].

Biological context of ELK1


Anatomical context of ELK1


Associations of ELK1 with chemical compounds

  • A phosphospecific antibody, Europium-labeled secondary antibody, and a time-resolved fluorescent readout were used to measure phosphorylation of ELK1 [18].
  • Expression of constitutively activated calcineurin or activation of endogenous calcineurin by Ca2+ ionophore decreased the phosphorylation of Elk1 at sites that positively regulate its transcriptional activity [19].
  • Calcineurin specifically dephosphorylates Elk1 at phosphoserine 383, a site whose phosphorylation by MAP kinases makes a critical contribution to the enhanced transcriptional activity of Elk1 [19].
  • Bradykinin-induced long-term effects on mitogenic signalling monitored by measuring the transcriptional activity of Elk1 were identical in cells expressing the wild-type or mutant B2 receptors [20].
  • This protein, ELK-1, and SAP-1 shared some unique structural properties such as an Ets DNA-binding site in the amino-terminal region, a serum response factor interacting domain and phosphorylation sites of serine or threonine residues in the carboxy-terminal region [21].

Physical interactions of ELK1

  • ELK1 and SAP1a have been shown to form ternary complexes with SRF on the SRE located in the c-fos promoter [22].

Regulatory relationships of ELK1


Other interactions of ELK1

  • These derivatives show that ZNF81 and ZNF21 lie within an approximately 130-kb segment and that SYN1.2 and ELK1 are less than 50 kb apart [25].
  • The localization of the DNA-binding domain of the protein at the N-terminus and th repression domain at the C-terminus is reminiscent of the organization of ELK1-like members of the ets family; however, there is no significant homology between ERF and ELK1 or any other ets member outside the DNA-binding domain [26].
  • There was also increased expression of phosphorylated MEK1/2 and Elk1 in the transformant cells [27].
  • In a systematic search for novel genes, we identified a novel transcript, UXT (HGMW-approved symbol), close to the ELK1 locus in Xp11.23-p11.22 [28].
  • Furthermore, E2 rapidly phosphorylated both CREB and ELK1, transcription factors that bind to the c-fos promoter and stimulate transcription [29].

Analytical, diagnostic and therapeutic context of ELK1


  1. A 5'-distal enhanceosome in the PDGF-A gene is activated in choriocarcinoma cells via ligand-independent binding of vitamin D receptor and constitutive jun kinase signaling. Pedigo, N.G., Zhang, H., Bruno, M.E., Kaetzel, C.S., Dugan, A.R., Shanehsaz, P., Hennigan, R.F., Xing, Z., Koszewski, N.J., Kaetzel, D.M. Oncogene (2005) [Pubmed]
  2. X-linked mental retardation: a comprehensive molecular screen of 47 candidate genes from a 7.4 Mb interval in Xp11. Jensen, L.R., Lenzner, S., Moser, B., Freude, K., Tzschach, A., Wei, C., Fryns, J.P., Chelly, J., Turner, G., Moraine, C., Hamel, B., Ropers, H.H., Kuss, A.W. Eur. J. Hum. Genet. (2007) [Pubmed]
  3. Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types. Chan, Y.J., Chiou, C.J., Huang, Q., Hayward, G.S. J. Virol. (1996) [Pubmed]
  4. Functional consequences of mutations in a putative Akt phosphorylation motif of B-raf in human cancers. Ikenoue, T., Kanai, F., Hikiba, Y., Tanaka, Y., Imamura, J., Ohta, M., Jazag, A., Guleng, B., Asaoka, Y., Tateishi, K., Kawakami, T., Matsumura, M., Kawabe, T., Omata, M. Mol. Carcinog. (2005) [Pubmed]
  5. A high throughput system for the evaluation of protein kinase C inhibitors based on Elk1 transcriptional activation in human astrocytoma cells. Sharif, T.R., Sharif, M. Int. J. Oncol. (1999) [Pubmed]
  6. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. Cohen-Armon, M., Visochek, L., Rozensal, D., Kalal, A., Geistrikh, I., Klein, R., Bendetz-Nezer, S., Yao, Z., Seger, R. Mol. Cell (2007) [Pubmed]
  7. Helicobacter pylori CagA protein activates serum response element-driven transcription independently of tyrosine phosphorylation. Hirata, Y., Maeda, S., Mitsuno, Y., Tateishi, K., Yanai, A., Akanuma, M., Yoshida, H., Kawabe, T., Shiratori, Y., Omata, M. Gastroenterology (2002) [Pubmed]
  8. Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry. Brunet, A., Roux, D., Lenormand, P., Dowd, S., Keyse, S., Pouysségur, J. EMBO J. (1999) [Pubmed]
  9. CpG-rich sequences close to the site of duplication within the human IGH constant region. Sadhu, A., Shen, M.L., Hackbarth, M., Hume, E., McKeithan, T.W. Immunogenetics (1997) [Pubmed]
  10. Structural organization of the human Elk1 gene and its processed pseudogene Elk2. Yamauchi, T., Toko, M., Suga, M., Hatakeyama, T., Isobe, M. DNA Res. (1999) [Pubmed]
  11. Egr-1 is activated by 17beta-estradiol in MCF-7 cells by mitogen-activated protein kinase-dependent phosphorylation of ELK-1. Chen, C.C., Lee, W.R., Safe, S. J. Cell. Biochem. (2004) [Pubmed]
  12. Mouse Elk oncogene maps to chromosome X and a novel Elk oncogene (Elk3) maps to chromosome 10. Tamai, Y., Taketo, M., Nozaki, M., Seldin, M.F. Genomics (1995) [Pubmed]
  13. Analysis of SRF, SAP-1 and ELK-1 transcripts and proteins in human cell lines. Magnaghi-Jaulin, L., Masutani, H., Lipinski, M., Harel-Bellan, A. FEBS Lett. (1996) [Pubmed]
  14. A novel human zinc finger protein ZNF540 interacts with MVP and inhibits transcriptional activities of the ERK signal pathway. Xiang, Z., Yuan, W., Luo, N., Wang, Y., Tan, K., Deng, Y., Zhou, X., Zhu, C., Li, Y., Liu, M., Wu, X., Li, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. Specificity in stress response: epidermal keratinocytes exhibit specialized UV-responsive signal transduction pathways. Adachi, M., Gazel, A., Pintucci, G., Shuck, A., Shifteh, S., Ginsburg, D., Rao, L.S., Kaneko, T., Freedberg, I.M., Tamaki, K., Blumenberg, M. DNA Cell Biol. (2003) [Pubmed]
  16. The roles of supernumerical X chromosomes and XIST expression in testicular germ cell tumors. Kawakami, T., Okamoto, K., Sugihara, H., Hattori, T., Reeve, A.E., Ogawa, O., Okada, Y. J. Urol. (2003) [Pubmed]
  17. Ethanol-induced modulation of hepatocellular extracellular signal-regulated kinase-1/2 activity via 4-hydroxynonenal. Sampey, B.P., Stewart, B.J., Petersen, D.R. J. Biol. Chem. (2007) [Pubmed]
  18. Identification of inhibitors of the kinase activity of oncogenic V600E BRAF in an enzyme cascade high-throughput screen. Newbatt, Y., Burns, S., Hayward, R., Whittaker, S., Kirk, R., Marshall, C., Springer, C., McDonald, E., Marais, R., Workman, P., Aherne, W. Journal of biomolecular screening : the official journal of the Society for Biomolecular Screening. (2006) [Pubmed]
  19. Stimulation of Elk1 transcriptional activity by mitogen-activated protein kinases is negatively regulated by protein phosphatase 2B (calcineurin). Tian, J., Karin, M. J. Biol. Chem. (1999) [Pubmed]
  20. Activation of mitogen-activated protein kinase by the bradykinin B2 receptor is independent of receptor phosphorylation and phosphorylation-triggered internalization. Blaukat, A., Pizard, A., Rajerison, R.M., Alhenc-Gelas, F., Müller-Esterl, W., Dikic, I. FEBS Lett. (1999) [Pubmed]
  21. Molecular cloning of Elk-3, a new member of the Ets family expressed during mouse embryogenesis and analysis of its transcriptional repression activity. Nozaki, M., Onishi, Y., Kanno, N., Ono, Y., Fujimura, Y. DNA Cell Biol. (1996) [Pubmed]
  22. FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements. Watson, D.K., Robinson, L., Hodge, D.R., Kola, I., Papas, T.S., Seth, A. Oncogene (1997) [Pubmed]
  23. Independent and cooperative activation of chromosomal c-fos promoter by STAT3. Yang, E., Lerner, L., Besser, D., Darnell, J.E. J. Biol. Chem. (2003) [Pubmed]
  24. RIP2 is a Raf1-activated mitogen-activated protein kinase kinase. Navas, T.A., Baldwin, D.T., Stewart, T.A. J. Biol. Chem. (1999) [Pubmed]
  25. Physical mapping in a YAC contig of 11 markers on the human X chromosome in Xp11.23. Hagemann, T., Surosky, R., Monaco, A.P., Lehrach, H., Rosen, F.S., Kwan, S.P. Genomics (1994) [Pubmed]
  26. ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation. Sgouras, D.N., Athanasiou, M.A., Beal, G.J., Fisher, R.J., Blair, D.G., Mavrothalassitis, G.J. EMBO J. (1995) [Pubmed]
  27. Mechanisms of acquired androgen independence during arsenic-induced malignant transformation of human prostate epithelial cells. Benbrahim-Tallaa, L., Webber, M.M., Waalkes, M.P. Environ. Health Perspect. (2007) [Pubmed]
  28. Cloning and characterization of UXT, a novel gene in human Xp11, which is widely and abundantly expressed in tumor tissue. Schroer, A., Schneider, S., Ropers, H., Nothwang, H. Genomics (1999) [Pubmed]
  29. 17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells. Hennessy, B.A., Harvey, B.J., Healy, V. Mol. Cell. Endocrinol. (2005) [Pubmed]
  30. Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor. Li, Q., Vaingankar, S.M., Green, H.M., Martins-Green, M. J. Biol. Chem. (1999) [Pubmed]
  31. Modified structure of the human serotonin transporter promoter. Flattem, N.L., Blakely, R.D. Mol. Psychiatry (2000) [Pubmed]
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