Disease relevance of CtBP

• Human CtBP attenuates transcriptional activation and tumorigenesis mediated by the adenovirus E1A protein [1].

High impact information on CtBP

• By contrast, the co-repressor proteins Groucho and dCtBP, and the histone deacetylase Rpd3, do not affect establishment but instead maintain repression after the blastoderm stage [2].
• YY1 DNA binding and PcG recruitment requires CtBP [3].
• Here we show that, in vitro, H directly binds two corepressor proteins, Groucho (Gro) and dCtBP [4].
• Human CtBP is a cellular phosphoprotein that interacts with the C-terminus of the adenovirus E1a oncoprotein and functions as a tumor suppressor. dCtBP also interacts with E1a in a directed yeast two-hybrid assay [5].
• While Hairy is probably not the only segmentation gene interacting with dCtBP, we show dose-sensitive genetic interactions between dCtBP and hairy mutations [5].

Biological context of CtBP

• The requirement for CtBP at certain enhancers appears to reflect the need for overall higher levels of repression, rather than a requirement for an activity unique to CtBP [6].
• In the study described here we have examined the structures of synthetic peptides identical to the CtBP binding sites on these proteins using NMR spectroscopy [7].
• C-Terminal binding protein (CtBP) interacts with a highly conserved amino acid motif (PXDLS) at the C terminus of adenovirus early region 1A (AdE1A) protein [7].
• Reduction of gro or dCtBP function enhances H mutant phenotypes and suppresses N phenotypes in the adult mechanosensory bristle [4].
• These observations raise the possibility that CtBP proteins might regulate gene expression directly by means of their enzymatic activities, in addition to serving as simple bridging proteins [8].

Anatomical context of CtBP

• This unique property of Snail in mesoderm formation can be attributed mostly to the CtBP co-repressor interaction motifs in the N-terminus, not to the C-terminal DNA-binding zinc fingers [9].
• Mutation of the dCtBP co-repressor interaction motifs in the Snail protein leads to reduction of the Snail function in central nervous system [10].

Associations of CtBP with chemical compounds

• Our results also show that repression by TTK69 of GAGA-dependent activation of the eve promoter is not mediated by any of the co-repressors known to interact with TTK69 (dMi2 or C-terminal binding protein) or by trichostatin A-sensitive histone deacetylases [11].

Physical interactions of CtBP

• CtIP, Snail (N-terminal peptide) and Knirps peptides all bind to mammalian CtBP with high affinity (K(i) of 1.04, 1.34 and 0.52 microM, respectively) [7].
• It has been shown that peptides identical to the CtBP binding site in CtIP and at the N terminus of Snail form a series of beta-turns similar to those seen in AdE1A [7].
• Here, we present evidence that Giant might also interact with dCtBP [12].
• The dCtBP binding motif of Hairless is essential for the function of Hairless in vivo [13].
• A dCtBP consensus binding motif in the C terminus appears to contribute to Ttk69 activity, but it cannot be fully responsible for the function of the C terminus [14].

Other interactions of CtBP

• Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors [15].
• Finally, we define crucial roles for the adaptor protein Hairless and the co-repressors Groucho and CtBP in conferring repressive activity on Su(H) in the SOP [16].
• Drosophila CtBP: a Hairy-interacting protein required for embryonic segmentation and hairy-mediated transcriptional repression [5].
• CtBP-dependent activities of the short-range Giant repressor in the Drosophila embryo [12].
• The Drosophila Knirps protein is a short-range transcriptional repressor that locally inhibits activators by recruiting the CtBP co-repressor [6].

Analytical, diagnostic and therapeutic context of CtBP

• The affinities of peptides for Drosophila and mammalian CtBP were compared using enzyme-linked immunosorbent assay [7].
• The CtBP THAP domain contains a large, positively charged surface patch and we demonstrate that this domain can bind to double-stranded DNA in an electrophoretic mobility-shift assay [17].

References