Corepressor CtBP1 interacts with and specifically inhibits CBP activity.
Transcription repression in eukaryotes is mediated by a wide variety of transcription factors that usually recruit corepressors and form corepressor complexes at the specific promoter sites. One of these corepressors is the C-terminal-binding protein (CtBP) which was first identified as a protein that binds to the C-terminal region of the adenovirus E1A protein. CtBP has a strong role in both development and oncogenesis. Till date, the mechanism of transcription repression by CtBP is unknown. Here, we report that CtBP physically interacts in vivo with HAT enzymes from different families. The vast majority of the HAT enzymes have a potential consensus site for CtBP binding within the bromodomain but we show that additional site(s) exists for CBP. The interaction between CtBP and CBP is functionally important and leads to impairment of histone H3 acetylation by CBP at specific lysine residues (Lys9, Lys14, and Lys18) in a dose-dependent and NADH-dependent manner. Based on these results, we propose that CtBP1 mediates repression by blocking histone acetylation by HAT complexes.
Senyuk
Vitalyi
V
Department of Pathology, The Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
Sinha
Kislay Kumar
KK
Nucifora
Giuseppina
G
D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D001665:Binding Sites; D050882:CREB-Binding Protein; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D015534:Trans-Activators; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D050882:CREB-Binding Protein; C494363:CREBBP protein, human