2rt5 | pdb_00002rt5
Structural insights into the recruitment of SMRT by the co-repressor SHARP under phosphorylative regulation
Structural highlights
FunctionMINT_HUMAN May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.[1] [2] Publication Abstract from PubMedThe transcriptional corepressors SMRT/NCoR, components of histone deacetylase complexes, interact with nuclear receptors and many other transcription factors. SMRT is a target for the ubiquitously expressed protein kinase CK2, which is known to phosphorylate a wide variety of substrates. Increasing evidence suggests that CK2 plays a regulatory role in many cellular events, particularly, in transcription. However, little is known about the precise mode of action involved. Here, we report the three-dimensional structure of a SMRT/HDAC1-associated repressor protein (SHARP) in complex with phosphorylated SMRT, as determined by solution NMR. Phosphorylation of the CK2 site on SMRT significantly increased affinity for SHARP. We also confirmed the significance of CK2 phosphorylation by reporter assay and propose a mechanism involving the process of phosphorylation acting as a molecular switch. Finally, we propose that the SPOC domain functions as a phosphorylation binding module. Structural Insights into the Recruitment of SMRT by the Corepressor SHARP under Phosphorylative Regulation.,Mikami S, Kanaba T, Takizawa N, Kobayashi A, Maesaki R, Fujiwara T, Ito Y, Mishima M Structure. 2013 Nov 19. pii: S0969-2126(13)00400-0. doi:, 10.1016/j.str.2013.10.007. PMID:24268649[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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