Changes in C-terminal binding protein 2 (CtBP2) corepressor complex induced by E1A and modulation of E1A transcriptional activity by CtBP2.
The N-terminal region of adenovirus E1A interacts with histone acetyl transferases (HATs) such as p300, P/CAF, and GCN5. The C-terminal region interacts with the transcriptional corepressors CtBP1 and CtBP2. The functional significance of co-recruitment of HATs and CtBPs by E1A is not well understood. In this study, we have shown that E1A enhanced acetylation of CtBP2 by recruitment of p300 to the CtBP2 complex. Additionally, E1A also displaced the histone methyltransferase G9a and the E-box repressor ZEB from the CtBP2 complex through the C-terminal CtBP-binding domain. A transcriptional activation function encoded by the E1A N-terminal region was efficiently inhibited by CtBP2 but not by a mutant with an N-terminal deletion or by a mutant deficient in interaction with E1A. Two isoforms of CtBP1 (CtBP1-L and CtBP1-S) poorly inhibited transcriptional activity of the E1A N-terminal region. Thus, the N-terminal domain of CtBP2 may contribute a unique transcriptional regulatory activity of CtBP2. Our results provide new insights by which CtBP might modulate the biochemical activities of E1A.
Zhao
Ling-Jun
LJ
Institute for Molecular Virology, Saint Louis University Health Sciences Center, St. Louis, Missouri 63110, USA.
Subramanian
T
T
Chinnadurai
G
G
D000107:Acetylation; D017500:Adenovirus E1A Proteins / Q000737:chemistry* / Q000378:metabolism; D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D000818:Animals; D056970:Co-Repressor Proteins; D005136:Eye Proteins / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D020033:Protein Isoforms; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D056970:Co-Repressor Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D050880:p300-CBP Transcription Factors