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Molecular and Cellular Biology, March 2006, p. 1917-1931, Vol. 26, No. 5
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.5.1917-1931.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

RBP1 Family Proteins Exhibit SUMOylation-Dependent Transcriptional Repression and Induce Cell Growth Inhibition Reminiscent of Senescence{dagger}

Olivier Binda,1 Jean-Sébastien Roy,1 and Philip E. Branton1,2,3*

Department of Biochemistry,1 Department of Oncology,2 McGill Cancer Center, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada3

Received 29 June 2005/ Returned for modification 23 August 2005/ Accepted 5 December 2005

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 (R1{sigma}) and a predicted {alpha}-helical region (R1{alpha}). R1{alpha} is embedded within the ARID region and represses basal transcription only, whereas R1{sigma} 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.


* Corresponding author. Mailing address: Department of Biochemistry, McGill University, McIntyre Medical Bldg., Rm. 702, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada. Phone: (514) 398-8350. Fax: (514) 398-8845. E-mail: philip.branton{at}mcgill.ca.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, March 2006, p. 1917-1931, Vol. 26, No. 5
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.5.1917-1931.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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