Acetylation control of the retinoblastoma tumour-suppressor protein.

The retinoblastoma tumour-suppressor protein (pRb) and p300/CBP co-activator proteins are important for control of proliferation and in tumour cells these are sequestered by viral oncoproteins such as E1A. pRb is involved in negatively regulating growth, and p300/CBP proteins have histone acetyltransferase (HAT) activity, which influences gene expression. Although it is ...
known that phosphorylation by G1 cyclin-dependent kinases (CDKs) regulates pRb activity, the nature and role of other post-translational modifications is not understood. Here we identify acetylation as a new type of modification and level of control in pRb function. Adenovirus E1A, which binds p300/CBP through an amino-terminal transformation-sensitive domain, stimulates the acetylation of pRb by recruiting p300 and pRb into a multimeric-protein complex. Furthermore, pRb acetylation is under cell-cycle control, and acetylation hinders the phosphorylation of pRb by cyclin-dependent kinases. pRb binds more strongly when acetylated to the MDM2 oncoprotein, which indicates that acetylation may regulate protein-protein interactions in the pRb pathway. The acetylation of pRb defines a new level of cell-cycle control mediated by HAT. Furthermore, our results establish a relationship between p300, pRb and acetylation in which E1A acts to recruit and target a cellular HAT activity to pRb.
Mesh Terms:
Acetylation, Adenovirus E1A Proteins, Cell Cycle, Growth Inhibitors, Humans, Mutation, Nuclear Proteins, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Retinoblastoma Protein, Trans-Activators, Transfection, Tumor Cells, Cultured
Nat. Cell Biol.
Date: Jul. 01, 2001
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