Lysine methylation regulates the pRb tumour suppressor protein

Oncogene. 2010 Apr 22;29(16):2357-67. doi: 10.1038/onc.2009.511. Epub 2010 Feb 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Differentiation
  • Cell Line, Tumor
  • Chromosomal Proteins, Non-Histone / metabolism
  • Humans
  • Lysine / metabolism*
  • Methylation
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / physiology*

Substances

  • Chromosomal Proteins, Non-Histone
  • Retinoblastoma Protein
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • Lysine