TORCs: transducers of regulated CREB activity - PubMed (original) (raw)
TORCs: transducers of regulated CREB activity
Michael D Conkright et al. Mol Cell. 2003 Aug.
Free article
Abstract
The cAMP responsive factor CREB stimulates gene expression, following its phosphorylation at Ser133, via recruitment of the coactivator CBP. In certain cell types, CREB also functions as a constitutive activator, although the underlying mechanisms are not understood. Here, we characterize a conserved family of coactivators, designated TORCs, for Transducers of Regulated CREB activity, that enhances CRE-dependent transcription via a phosphorylation-independent interaction with the bZIP DNA binding/dimerization domain of CREB. TORC recruitment does not appear to modulate CREB DNA binding activity, but rather enhances the interaction of CREB with the TAF(II)130 component of TFIID following its recruitment to the promoter. Remarkably, in certain mucoepidermoid carcinomas, a chromosomal translocation fuses the CREB binding domain of TORC1 to the Notch coactivator Mastermind (MAML2). As expression of the TORC1-MAML2 chimera strongly induced target gene expression via CREB, our results reveal a mechanism by which CREB stimulates transcription in normal and transformed cells.
Similar articles
- Chromatin-dependent cooperativity between constitutive and inducible activation domains in CREB.
Asahara H, Santoso B, Guzman E, Du K, Cole PA, Davidson I, Montminy M. Asahara H, et al. Mol Cell Biol. 2001 Dec;21(23):7892-900. doi: 10.1128/MCB.21.23.7892-7900.2001. Mol Cell Biol. 2001. PMID: 11689682 Free PMC article. - Molecular Basis for the Mechanism of Constitutive CBP/p300 Coactivator Recruitment by CRTC1-MAML2 and Its Implications in cAMP Signaling.
Clark MD, Kumar GS, Marcum R, Luo Q, Zhang Y, Radhakrishnan I. Clark MD, et al. Biochemistry. 2015 Sep 8;54(35):5439-46. doi: 10.1021/acs.biochem.5b00332. Epub 2015 Aug 21. Biochemistry. 2015. PMID: 26274502 Free PMC article. - Magnitude of the CREB-dependent transcriptional response is determined by the strength of the interaction between the kinase-inducible domain of CREB and the KIX domain of CREB-binding protein.
Shaywitz AJ, Dove SL, Kornhauser JM, Hochschild A, Greenberg ME. Shaywitz AJ, et al. Mol Cell Biol. 2000 Dec;20(24):9409-22. doi: 10.1128/MCB.20.24.9409-9422.2000. Mol Cell Biol. 2000. PMID: 11094091 Free PMC article. - Regulation of somatostatin gene transcription by cyclic adenosine monophosphate.
Montminy M, Brindle P, Arias J, Ferreri K, Armstrong R. Montminy M, et al. Metabolism. 1996 Aug;45(8 Suppl 1):4-7. doi: 10.1016/s0026-0495(96)90068-2. Metabolism. 1996. PMID: 8769368 Review. - What turns CREB on?
Johannessen M, Delghandi MP, Moens U. Johannessen M, et al. Cell Signal. 2004 Nov;16(11):1211-27. doi: 10.1016/j.cellsig.2004.05.001. Cell Signal. 2004. PMID: 15337521 Review.
Cited by
- Single-Molecule Imaging Reveals Dynamics of CREB Transcription Factor Bound to Its Target Sequence.
Sugo N, Morimatsu M, Arai Y, Kousoku Y, Ohkuni A, Nomura T, Yanagida T, Yamamoto N. Sugo N, et al. Sci Rep. 2015 Jun 3;5:10662. doi: 10.1038/srep10662. Sci Rep. 2015. PMID: 26039515 Free PMC article. - Biological functions of CRTC2 and its role in metabolism-related diseases.
Zheng HY, Wang YX, Zhou K, Xie HL, Ren Z, Liu HT, Ou YS, Zhou ZX, Jiang ZS. Zheng HY, et al. J Cell Commun Signal. 2023 Sep;17(3):495-506. doi: 10.1007/s12079-023-00730-5. Epub 2023 Mar 1. J Cell Commun Signal. 2023. PMID: 36856929 Free PMC article. Review. - A role for the CREB co-activator CRTC2 in the hypothalamic mechanisms linking glucose sensing with gene regulation.
Lerner RG, Depatie C, Rutter GA, Screaton RA, Balthasar N. Lerner RG, et al. EMBO Rep. 2009 Oct;10(10):1175-81. doi: 10.1038/embor.2009.177. Epub 2009 Aug 28. EMBO Rep. 2009. PMID: 19713961 Free PMC article. - Regulation of Liver Glucose and Lipid Metabolism by Transcriptional Factors and Coactivators.
Ramatchandirin B, Pearah A, He L. Ramatchandirin B, et al. Life (Basel). 2023 Feb 13;13(2):515. doi: 10.3390/life13020515. Life (Basel). 2023. PMID: 36836874 Free PMC article. Review. - The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis.
Wang Y, Vera L, Fischer WH, Montminy M. Wang Y, et al. Nature. 2009 Jul 23;460(7254):534-7. doi: 10.1038/nature08111. Epub 2009 Jun 21. Nature. 2009. PMID: 19543265 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials