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PMID: 7760821 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Direct transcriptional repression by pRB and its reversal by specific cyclins.

Molecular and cellular biology ·Vol. 15 ·No. 6 ·1995-06-00 ·Pages 3256-65

Bremner R, Cohen BL, Sopta M, Hamel PA, Ingles CJ, Gallie BL, Phillips RA

Abstract

It was recently shown that the E2F-pRB complex is a negative transcriptional regulator. However, it was not determined whether the whole complex or pRB alone is required for repression. Here we show that pRB and the related protein p107 are capable of direct transcriptional repression independent of E2F. When fused to the DNA binding domain of GAL4, pRB or p107 represses transcription of promoters with GAL4 binding sites. Thus, E2F acts as a tether for pRB or p107 but is not actively involved in repression of other enhancers. This function of pRB maps to the pocket and is abrogated by mutation of this domain. This result suggests an intriguing model in which the pocket has a dual function, first to bind E2F and second to repress transcription directly, possibly through interaction with other proteins. We also show that direct transcriptional repression by pRB is regulated by phosphorylation. Mutations which render pRB constitutively hypophosphorylated potentiate repression, while phosphorylation induced by cyclin A or E reduces repression ninefold.

MeSH Terms
Base Sequence Cell Line Cyclins/metabolism,pharmacology Gene Expression Regulation, Neoplastic Genes, Retinoblastoma/genetics Humans Molecular Sequence Data Recombinant Fusion Proteins/metabolism Retinoblastoma Protein/metabolism,pharmacology Transcription, Genetic/drug effects
Chemicals
Cyclins Recombinant Fusion Proteins Retinoblastoma Protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bremner R
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Canada.
Cohen B L
Sopta M
Hamel P A
Ingles C J
Gallie B L
Phillips R A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.6.3256
Published
1995-06-00
Pages
3256-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230558
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.15.6.3256 PMC Full Text View journal details
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