title: Ubiquitination of retinoblastoma family protein 1 potentiates gene-specific repression function.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Raj
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Wei
authors.forename: David N
authors.initials: DN
authors.lastname: Arnosti
authors.forename: R William
authors.initials: RW
authors.lastname: Henry
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation / Q000502:physiology; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C099965:Rbf protein, Drosophila; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors