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

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.

journal_name

Mol Cell Biol

authors

Binda O,Roy JS,Branton PE

doi

10.1128/MCB.26.5.1917-1931.2006

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

1917-31

issue

5

eissn

0270-7306

issn

1098-5549

pii

26/5/1917

journal_volume

26

pub_type

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