The reference OMIM entry for this protein is 602618

C-terminal-binding protein 1; ctbp1

CLONING

The E1a region of group C adenoviruses encodes 2 nearly identical proteins that are largely responsible for the oncogenic properties of adenoviruses. Whereas the N-terminal half of these E1A proteins is sufficient for transformation, the C-terminal half appears to modulate transformation, tumorigenesis, and metastasis negatively. Boyd et al. (1993) purified a HeLa cell protein, designated CTBP1, that specifically binds to the C-terminal half of E1A proteins. CTBP1 is a phosphoprotein that migrates as a 48-kD doublet by SDS-PAGE. Katsanis and Fisher (1998) suggested that the doublet consists of CTBP1 and the closely related CTBP2 (602619). Schaeper et al. (1995) independently isolated a CTBP1 cDNA from a B-cell library. The predicted 439-amino acid sequence contains the sequences of 2 peptides prepared from purified CTBP1. The authors coimmunoprecipitated CTPB1 and an E1A protein from extracts of mammalian cells that were expressing both proteins. Furusawa et al. (1999) identified the mouse homologs of CTBP1 and CTBP2 in a yeast 2-hybrid screen for proteins that interact with delta-EF1 (TCF8; 189909), a transcriptional repressor that binds the E2-box (CACCTG) and related sequences. Using 2-hybrid and direct binding assays, they concluded that CtBP1 binds to the short medial portion of delta-EF1 containing the PLDLSL motif. In cotransfection experiments, they observed that CtBP1 enhanced the transrepression activity of delta-EF1. Using Northern blot analysis and in situ hybridization with mouse embryos, Furusawa et al. (1999) detected CtBP1 expression throughout developmental stages and in a wide range of adult tissues. CtBP1 and CtBP2 expression correlates with delta-EF1 expression. The authors hypothesized that CtBP1 and CtBP2 function as corepressors of delta-EF1 action.

GENE FUNCTION

Polycomb (Pc) is part of a Pc group (PcG) protein complex that is involved in repression of gene activity during Drosophila and vertebrate development. Using a yeast 2-hybrid assay, Sewalt et al. (1999) found that Xenopus Ctbp1 interacts with Xenopus Pc and that human CTBP2 interacts with PC2 (603079), a human Pc homolog. Immunofluorescence studies indicated that CTBP1 and CTBP2 partially colocalize with PC2 in large PcG domains in interphase nuclei. As with PC2, chimeric LexA-CTBP2 and LexA-CTBP1 proteins repressed gene activity when targeted to a reporter gene. Sewalt et al. (1999) suggested that PC2-mediated repression of gene expression involves an association with corepressors such as the CTBPs. They speculated that the interference of the adenoviral E1A protein with the transcription machinery of the infected cell may involve interference with PcG-mediated repression through disruption of the CTBP-PcG interaction. Northern blot analysis revealed that the CTBP1 gene was expressed as a 2.4-kb mRNA in all human tissues tested. Pc2 recruits the transcriptional corepressor CTBP to PcG bodies. Kagey et al. (2003) showed that CTBP is sumoylated at a single lysine. In vitro, CTBP sumoylation minimally required the SUMO E1 and E2 (UBC9; 601661) and SUMO1 (601912). However, Pc2 dramatically enhanced CTBP sumoylation. The authors proposed that, in vivo, this is likely due to the ability of Pc2 to recruit both CTBP and UBC9 to PcG bodies, thereby bringing together substrate and E2 and stimulating the transfer of SUMO to CTBP. These results demonstrated that Pc2 is a SUMO E3 and suggested that PcG bodies may be sumoylation centers. ... More on the omim web site

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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602618 was added.