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Molecular and Cellular Biology, September 2001, p. 6181-6188, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6181-6188.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Acetylation of Nuclear Hormone Receptor-Interacting Protein RIP140 Regulates Binding of the Transcriptional Corepressor CtBP

Ngan Vo, Clark Fjeld, and Richard H. Goodman*

Vollum Institute, Oregon Health Sciences University, Portland, Oregon

Received 27 March 2001/Returned for modification 22 April 2001/Accepted 19 June 2001

CtBP (carboxyl-terminal binding protein) participates in regulating cellular development and differentiation by associating with a diverse array of transcriptional repressors. Most of these interactions occur through a consensus CtBP-binding motif, PXDLS, in the repressor proteins. We previously showed that the CtBP-binding motif in E1A is flanked by a Lys residue and suggested that acetylation of this residue by the p300/CBP-associated factor P/CAF disrupts the CtBP interaction. In this study, we show that the interaction between CtBP and the nuclear hormone receptor corepressor RIP140 is regulated similarly, in this case by p300/CBP itself. CtBP was shown to interact with RIP140 in vitro and in vivo through a sequence, PIDLSCK, in the amino-terminal third of the RIP140 protein. Acetylation of the Lys residue in this motif, demonstrated in vivo by using an acetylated RIP140-specific antibody, dramatically reduced CtBP binding. Mutation of the Lys residue to Gln resulted in a decrease in CtBP binding in vivo and a loss of transcriptional repression. We suggest that p300/CBP-mediated acetylation disrupts the RIP140-CtBP complex and derepresses nuclear hormone receptor-regulated genes. Disruption of repressor-CtBP interactions by acetylation may be a general mode of gene activation.

* Corresponding author. Mailing address: Vollum Institute L-474, Oregon Health Sciences University, 3181 S.W. Sam Jackson Pk. Rd., Portland, OR 97201. Phone: (503) 494-5078. Fax: (503) 494-4353. E-mail: goodmanr{at}ohsu.edu.

Molecular and Cellular Biology, September 2001, p. 6181-6188, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6181-6188.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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