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J Biol Chem. 2012 Dec 7;287(50):41835-43. doi: 10.1074/jbc.M112.422428. Epub 2012 Oct 18.

Ubiquitination of retinoblastoma family protein 1 potentiates gene-specific repression function.

Author information

1
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319, USA.

Abstract

The retinoblastoma (RB) tumor suppressor family functions as a regulatory node governing cell cycle progression, differentiation, and apoptosis. Post-translational modifications play a critical role in modulating RB activity, but additional levels of control, including protein turnover, are also essential for proper function. The Drosophila RB homolog Rbf1 is subjected to developmentally cued proteolysis mediated by an instability element (IE) present in the C terminus of this protein. Paradoxically, instability mediated by the IE is also linked to Rbf1 repression potency, suggesting that proteolytic machinery may also be directly involved in transcriptional repression. We show that the Rbf1 IE is an autonomous degron that stimulates both Rbf1 ubiquitination and repression potency. Importantly, Rbf1 IE function is promoter-specific, contributing to repression of cell cycle responsive genes but not to repression of cell signaling genes. The multifunctional IE domain thus provides Rbf1 flexibility for discrimination between target genes embedded in divergent cellular processes.

PMID:
23086928
PMCID:
PMC3516731
DOI:
10.1074/jbc.M112.422428
[Indexed for MEDLINE]
Free PMC Article

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