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J. Biol. Chem., Vol. 281, Issue 48, 36613-36623, December 1, 2006

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Changes in C-terminal Binding Protein 2 (CtBP2) Corepressor Complex Induced by E1A and Modulation of E1A Transcriptional Activity by CtBP2^*

From the Institute for Molecular Virology, Saint Louis University Health Sciences Center, St. Louis, Missouri 63110

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.

Received for publication, April 12, 2006 , and in revised form, September 29, 2006.

^* This work was supported by NCI, National Institutes of Health Research Grants CA-84941 and CA-33616. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Institute for Molecular Virology, Saint Louis University Health Sciences Center, 3681 Park Ave., St. Louis, MO 63110. Tel.: 314-977-8794; Fax: 314-977-8798; E-mail: chinnag{at}slu.edu.

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