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Molecular and Cellular Biology, October 1999, p. 6632-6641, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

RBP1 Recruits Both Histone Deacetylase-Dependent and -Independent Repression Activities to Retinoblastoma Family Proteins

Albert Lai,1 Joseph M. Lee,1 Wen-Ming Yang,2 James A. DeCaprio,3 William G. Kaelin Jr.,3,4 Edward Seto,2 and Philip E. Branton1,5,*

Departments of Biochemistry1 and Oncology,5 McGill University, Montreal, Quebec, Canada H3G 1Y6; H. Lee Moffitt Cancer Center and Research Institute, Molecular Oncology Program, University of South Florida, Tampa, Florida 336122; and Dana-Farber Cancer Institute and Harvard Medical School3 and Howard Hughes Medical Institute,4 Boston, Massachusetts 02115

Received 3 May 1999/Returned for modification 1 June 1999/Accepted 18 June 1999

Retinoblastoma (RB) tumor suppressor family proteins block cell proliferation in part by repressing certain E2F-specific promoters. Both histone deacetylase (HDAC)-dependent and -independent repression activities are associated with the RB "pocket." The mechanism by which these two repression functions occupy the pocket is unknown. A known RB-binding protein, RBP1, was previously found by our group to be an active corepressor which, if overexpressed, represses E2F-mediated transcription via its association with the pocket. We show here that RBP1 contains two repression domains, one of which binds all three known HDACs and represses them in an HDAC-dependent manner while the other domain functions independently of the HDACs. Thus, RB family members repress transcription by recruiting RBP1 to the pocket. RBP1, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function.


* Corresponding author. Mailing address: Departments of Biochemistry and Oncology, McGill University, McIntyre Medical Building, 3655 Drummond St., Montreal, Quebec, Canada H3G 1Y6. Phone: (514) 398-7268. Fax: (514) 398-7384. E-mail: branton{at}med.mcgill.ca.


Molecular and Cellular Biology, October 1999, p. 6632-6641, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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