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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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