| Structural highlights
Function
[BCORL_HUMAN] Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence specific DNA-binding proteins such as BCL6. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor.[1] [PCGF1_HUMAN] Component of the Polycomb group (PcG) multiprotein BCOR complex, a complex required to maintain the transcriptionally repressive state of some genes, such as BCL6 and the cyclin-dependent kinase inhibitor, CDKN1A. Transcriptional repressor that may be targeted to the DNA by BCL6; this transcription repressor activity may be related to PKC signaling pathway. Represses CDKN1A expression by binding to its promoter, and this repression is dependent on the retinoic acid response element (RARE element). Promotes cell cycle progression and enhances cell proliferation as well. May have a positive role in tumor cell growth by down-regulating CDKN1A. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility.[2] [3] [4]
Publication Abstract from PubMed
Polycomb-group RING finger homologs (PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, and PCGF6) are critical components in the assembly of distinct Polycomb repression complex 1 (PRC1)-related complexes. Here, we identify a protein interaction domain in BCL6 corepressor, BCOR, which binds the RING finger- and WD40-associated ubiquitin-like (RAWUL) domain of PCGF1 (NSPC1) and PCGF3 but not of PCGF2 (MEL18) or PCGF4 (BMI1). Because of the selective binding, we have named this domain PCGF Ub-like fold discriminator (PUFD). The structure of BCOR PUFD bound to PCGF1 reveals that (1) PUFD binds to the same surfaces as observed for a different Polycomb group RAWUL domain and (2) the ability of PUFD to discriminate among RAWULs stems from the identity of specific residues within these interaction surfaces. These data show the molecular basis for determining the binding preference for a PCGF homolog, which ultimately helps determine the identity of the larger PRC1-like assembly.
Structure of the Polycomb Group Protein PCGF1 in Complex with BCOR Reveals Basis for Binding Selectivity of PCGF Homologs.,Junco SE, Wang R, Gaipa JC, Taylor AB, Schirf V, Gearhart MD, Bardwell VJ, Demeler B, Hart PJ, Kim CA Structure. 2013 Apr 2;21(4):665-71. doi: 10.1016/j.str.2013.02.013. Epub 2013 Mar, 21. PMID:23523425[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pagan JK, Arnold J, Hanchard KJ, Kumar R, Bruno T, Jones MJ, Richard DJ, Forrest A, Spurdle A, Verdin E, Crossley M, Fanciulli M, Chenevix-Trench G, Young DB, Khanna KK. A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP. J Biol Chem. 2007 May 18;282(20):15248-57. Epub 2007 Mar 22. PMID:17379597 doi:10.1074/jbc.M700246200
- ↑ Gong Y, Wang X, Liu J, Shi L, Yin B, Peng X, Qiang B, Yuan J. NSPc1, a mainly nuclear localized protein of novel PcG family members, has a transcription repression activity related to its PKC phosphorylation site at S183. FEBS Lett. 2005 Jan 3;579(1):115-21. PMID:15620699 doi:10.1016/j.febslet.2004.11.056
- ↑ Gearhart MD, Corcoran CM, Wamstad JA, Bardwell VJ. Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Mol Cell Biol. 2006 Sep;26(18):6880-9. PMID:16943429 doi:26/18/6880
- ↑ Gong Y, Yue J, Wu X, Wang X, Wen J, Lu L, Peng X, Qiang B, Yuan J. NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element. Nucleic Acids Res. 2006;34(21):6158-69. Epub 2006 Nov 6. PMID:17088287 doi:gkl834
- ↑ Junco SE, Wang R, Gaipa JC, Taylor AB, Schirf V, Gearhart MD, Bardwell VJ, Demeler B, Hart PJ, Kim CA. Structure of the Polycomb Group Protein PCGF1 in Complex with BCOR Reveals Basis for Binding Selectivity of PCGF Homologs. Structure. 2013 Apr 2;21(4):665-71. doi: 10.1016/j.str.2013.02.013. Epub 2013 Mar, 21. PMID:23523425 doi:http://dx.doi.org/10.1016/j.str.2013.02.013
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