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Acetylation regulates the differentiation-specific functions of the retinoblastoma protein.
Nguyen, Don X; Baglia, Laurel A; Huang, Shih-Min; Baker, Christina M; McCance, Dennis J.
Affiliation
  • Nguyen DX; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
EMBO J ; 23(7): 1609-18, 2004 Apr 07.
Article in En | MEDLINE | ID: mdl-15044952
The retinoblastoma tumor-suppressor protein (pRb) is known to induce growth arrest and cellular differentiation. The molecular determinants of pRb function include protein-protein interactions and post-translational modifications such as phosphorylation. Recently, the co-activator p300 was found to acetylate pRb. The biological significance of pRb acetylation, however, remains unclear. In the present study, we provide evidence that pRb undergoes acetylation upon cellular differentiation, including skeletal myogenesis. In addition to p300, the p300-Associated Factor (P/CAF) can mediate pRb acetylation as pRb interacts directly with the acetyltransferase domain of P/CAF in vitro and can associate with P/CAF in differentiated cells. Significantly, by using a C terminal acetylation-impaired mutant of pRb, we reveal that acetylation does not affect pRb-dependent growth arrest or the repression of E2F transcriptional activity. Instead, acetylation is required for pRb-mediated terminal cell cycle exit and the induction of late myogenic gene expression. Based on these results, we propose that acetylation regulates the differentiation-specific function(s) of pRb.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Acetyltransferases / Transcription Factors / Transcription, Genetic / Nuclear Proteins / Cell Differentiation / Trans-Activators / Gene Expression Regulation / Retinoblastoma Protein / Cell Cycle Proteins Limits: Animals / Humans Language: En Journal: EMBO J Year: 2004 Document type: Article Affiliation country: United States Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Acetyltransferases / Transcription Factors / Transcription, Genetic / Nuclear Proteins / Cell Differentiation / Trans-Activators / Gene Expression Regulation / Retinoblastoma Protein / Cell Cycle Proteins Limits: Animals / Humans Language: En Journal: EMBO J Year: 2004 Document type: Article Affiliation country: United States Country of publication: United kingdom