Lysine methylation regulates the pRb tumour suppressor protein.
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.
Department of Clinical Pharmacology, Medical Sciences Division, University of Oxford, Oxford, UK.
S
S
Munro
N
N
Khaire
A
A
Inche
S
S
Carr
N B
NB
La Thangue
D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D016160:Retinoblastoma Protein; D000090266:Chromobox Protein Homolog 5; D008239:Lysine