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Gene Review

CRTC1  -  CREB regulated transcription coactivator 1

Homo sapiens

Synonyms: FLJ14027, KIAA0616, MECT1, TORC-1, TORC1, ...
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Disease relevance of CRTC1


Psychiatry related information on CRTC1


High impact information on CRTC1

  • Our findings reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function [9].
  • The physiological consequences of mammalian TORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders [10].
  • MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product [11].
  • Loss of tumor suppressors TSC1 or TSC2 leads to aberrant activation of TORC1, which has been implicated in the control of cell size [3].
  • The transforming activity of MECT1-MAML2 was markedly reduced by blocking CREB DNA binding [12].

Biological context of CRTC1


Anatomical context of CRTC1

  • Recent studies in eukaryotic cells have identified two distinct TOR complexes, TORC1 and TORC2, which phosphorylate different substrates and have distinct physiological functions [17].
  • In addition, the RNAi-specific vector had no effect on colony growth of non-MEC tumors including a lung tumor or two other salivary gland cell lines that do not express Mect1-Maml2 [18].
  • The origin of MECT is unknown but the morphology of this tumour closely resembles features seen in the ultimobranchial body (UB) vestiges [5].

Associations of CRTC1 with chemical compounds

  • Biochemical and genetic analyses of these mutant forms of Tor1p support a model wherein functional interactions between the FRB and kinase domains, as well as between the FRB domain and the TORC1 component Kog1p, regulate TOR activity as well as contribute to the mechanism of caffeine resistance [19].
  • TOR signals through two physically distinct multiprotein complexes, and the control of cell growth is mediated primarily by TOR complex 1 (TORC1), which contains the polypeptides raptor and LST8 [20].

Enzymatic interactions of CRTC1


Other interactions of CRTC1


Analytical, diagnostic and therapeutic context of CRTC1

  • The patient had no significant affective episodes or hospitalizations during the 3 years of MECT [7].
  • In an attempt to clarify the putative relationship between MECT and PTC, we analysed tissue from 11 patients with MECT by immunohistochemistry (E-, P- and N-cadherins and alpha-, beta- and gamma-catenins) [24].
  • Further research is needed, however, to clarify the optimum use of MECT schedules and pharmacotherapy combinations to most effectively and safely prevent relapse of depression in different elderly populations and to help predict who will best respond to which treatment modalities [25].


  1. TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats. Siu, Y.T., Chin, K.T., Siu, K.L., Yee Wai Choy, E., Jeang, K.T., Jin, D.Y. J. Virol. (2006) [Pubmed]
  2. Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion. Behboudi, A., Winnes, M., Gorunova, L., van den Oord, J.J., Mertens, F., Enlund, F., Stenman, G. Genes Chromosomes Cancer (2005) [Pubmed]
  3. mTOR Pathway as a Target in Tissue Hypertrophy. Lee, C.H., Inoki, K., Guan, K.L. Annu. Rev. Pharmacol. Toxicol. (2007) [Pubmed]
  4. TORCs rev up gluconeogenesis. Patil, S., Unterman, T.G. Cell metabolism. (2005) [Pubmed]
  5. A study on the relationship between solid cell nests and mucoepidermoid carcinoma of the thyroid. Harach, H.R. Histopathology (1985) [Pubmed]
  6. Acute and maintenance ECT with flupenthixol in refractory schizophrenia: sustained improvements in psychopathology, quality of life, and social outcomes. Chanpattana, W., Kramer, B.A. Schizophr. Res. (2003) [Pubmed]
  7. A seasonal schedule for maintenance ECT. Kramer, B.A. The journal of ECT. (1999) [Pubmed]
  8. A review of continuation and maintenance electroconvulsive therapy. Rabheru, K., Persad, E. Canadian journal of psychiatry. Revue canadienne de psychiatrie. (1997) [Pubmed]
  9. SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity. Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S.Y., Huang, Q., Qin, J., Su, B. Cell (2006) [Pubmed]
  10. TOR signaling in growth and metabolism. Wullschleger, S., Loewith, R., Hall, M.N. Cell (2006) [Pubmed]
  11. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Tonon, G., Modi, S., Wu, L., Kubo, A., Coxon, A.B., Komiya, T., O'Neil, K., Stover, K., El-Naggar, A., Griffin, J.D., Kirsch, I.R., Kaye, F.J. Nat. Genet. (2003) [Pubmed]
  12. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. Wu, L., Liu, J., Gao, P., Nakamura, M., Cao, Y., Shen, H., Griffin, J.D. EMBO J. (2005) [Pubmed]
  13. Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. Iourgenko, V., Zhang, W., Mickanin, C., Daly, I., Jiang, C., Hexham, J.M., Orth, A.P., Miraglia, L., Meltzer, J., Garza, D., Chirn, G.W., McWhinnie, E., Cohen, D., Skelton, J., Terry, R., Yu, Y., Bodian, D., Buxton, F.P., Zhu, J., Song, C., Labow, M.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes. Coxon, A., Rozenblum, E., Park, Y.S., Joshi, N., Tsurutani, J., Dennis, P.A., Kirsch, I.R., Kaye, F.J. Cancer Res. (2005) [Pubmed]
  15. Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors. Enlund, F., Behboudi, A., Andrén, Y., Oberg, C., Lendahl, U., Mark, J., Stenman, G. Exp. Cell Res. (2004) [Pubmed]
  16. TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Yang, Q., Inoki, K., Kim, E., Guan, K.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Complexity of the TOR signaling network. Inoki, K., Guan, K.L. Trends Cell Biol. (2006) [Pubmed]
  18. Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Komiya, T., Park, Y., Modi, S., Coxon, A.B., Oh, H., Kaye, F.J. Oncogene (2006) [Pubmed]
  19. Caffeine Targets TOR Complex I and Provides Evidence for a Regulatory Link between the FRB and Kinase Domains of Tor1p. Reinke, A., Chen, J.C., Aronova, S., Powers, T. J. Biol. Chem. (2006) [Pubmed]
  20. Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Avruch, J., Hara, K., Lin, Y., Liu, M., Long, X., Ortiz-Vega, S., Yonezawa, K. Oncogene (2006) [Pubmed]
  21. Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade. Katoh, Y., Takemori, H., Lin, X.Z., Tamura, M., Muraoka, M., Satoh, T., Tsuchiya, Y., Min, L., Doi, J., Miyauchi, A., Witters, L.A., Nakamura, H., Okamoto, M. FEBS J. (2006) [Pubmed]
  22. Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1{alpha} transcription and mitochondrial biogenesis in muscle cells. Wu, Z., Huang, X., Feng, Y., Handschin, C., Feng, Y., Gullicksen, P.S., Bare, O., Labow, M., Spiegelman, B., Stevenson, S.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  23. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Liu, L., Li, F., Cardelli, J.A., Martin, K.A., Blenis, J., Huang, S. Oncogene (2006) [Pubmed]
  24. Mucoepidermoid carcinoma of the thyroid: a tumour histotype characterised by P-cadherin neoexpression and marked abnormalities of E-cadherin/catenins complex. Rocha, A.S., Soares, P., Machado, J.C., Máximo, V., Fonseca, E., Franssila, K., Sobrinho-Simões, M. Virchows Arch. (2002) [Pubmed]
  25. ECT in the elderly. Greenberg, R.M. New directions for mental health services. (1997) [Pubmed]
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