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PMID: 16479010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RBP1 family proteins exhibit SUMOylation-dependent transcriptional repression and induce cell growth inhibition reminiscent of senescence.

Molecular and cellular biology ·Vol. 26 ·No. 5 ·2006-03-00 ·Pages 1917-31

Binda O, Roy JS, Branton PE

Abstract

The retinoblastoma binding protein 1 (RBP1) appears to be an important factor in the repression of E2F-dependent transcription by the retinoblastoma protein (pRB) family. The recent identification of the breast carcinoma associated antigen (BCAA) as an RBP1-like protein led us to investigate its biological properties and compare them to RBP1. Like RBP1, BCAA contains a carboxy-terminal R2 domain that elicits histone deacetylase (HDAC)-dependent transcriptional repression via interactions with the SAP30 subunit of the Sin3/HDAC complex. Each RBP1 family member also contains two HDAC-independent repression activities within a region termed R1, which can be subdivided into a SUMOylated moiety (R1sigma) and a predicted alpha-helical region (R1alpha). R1alpha is embedded within the ARID region and represses basal transcription only, whereas R1sigma represses both basal and activated transcription and depends on SUMOylation. Overexpression of either RBP1 or BCAA, but not the truncated BCAAMCF-7 isoform that is overexpressed in breast cancer cells, caused a profound inhibition of cell proliferation and induced expression of a senescence marker. In each case the presence of both R1 and R2 was necessary for suppression of cell growth, suggesting that both R1 and R2 transcriptional repression activities play a role in RBP1 family protein-mediated regulation of cellular proliferation.

MeSH Terms
Amino Acid Sequence Animals Antigens, Neoplasm/genetics,metabolism Binding Sites CHO Cells Carrier Proteins/genetics,metabolism Cell Proliferation Cellular Senescence/physiology Cricetinae Cricetulus Gene Expression Regulation Histone Deacetylases/genetics,metabolism Humans Molecular Sequence Data Mutation Protein Structure, Tertiary Repressor Proteins/genetics,metabolism Retinoblastoma-Binding Protein 1 SUMO-1 Protein/metabolism Sequence Homology, Amino Acid Transcription, Genetic Tumor Cells, Cultured
Chemicals
Antigens, Neoplasm Carrier Proteins Repressor Proteins Retinoblastoma-Binding Protein 1 SAP30 protein, human SUMO-1 Protein Histone Deacetylases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Binda Olivier
Department of Biochemistry, McGill University, McIntyre Medical Bldg., Rm. 702, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada. philip.branton@mcgill.ca.
Roy Jean-Sébastien
Branton Philip E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.5.1917-1931.2006
Email
philip.branton@mcgill.ca
Published
2006-03-00
Pages
1917-31
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1430237
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.26.5.1917-1931.2006 PMC Full Text View journal details
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