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.
Munro
S
S
Department of Clinical Pharmacology, Medical Sciences Division, University of Oxford, Oxford, UK.
Khaire
N
N
Inche
A
A
Carr
S
S
La Thangue
N B
NB
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