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The pRb tumour suppressor protein has a central role in coordinating early cell cycle progression. An important level of control imposed on pRb occurs through post-translational modification, for example, phosphorylation. We describe here a new level of regulation on pRb, mediated through the targeted methylation of lysine residues, by the methyltransferase Set7/9. Set7/9 methylates the C-terminal region of pRb, both in vitro and in cells, and methylated pRb interacts with heterochromatin protein HP1. pRb methylation is required for pRb-dependent cell cycle arrest and transcriptional repression, as well as pRb-dependent differentiation. Our results indicate that methylation can influence the properties of pRb, and raise the interesting possibility that methylation modulates pRb tumour suppressor activity.

Original publication

DOI

10.1038/onc.2009.511

Type

Journal article

Journal

Oncogene

Publication Date

22/04/2010

Volume

29

Pages

2357 - 2367

Keywords

Cell Cycle, Cell Differentiation, Cell Line, Tumor, Chromosomal Proteins, Non-Histone, Humans, Lysine, Methylation, Retinoblastoma Protein