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Lysine methylation regulates the pRb tumour suppressor protein

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.

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Acknowledgements

We thank the CRUK, EU, LRF, MRC and AICR for supporting this work and R Williams for assistance in preparing the paper.

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Correspondence to N B La Thangue.

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Munro, S., Khaire, N., Inche, A. et al. Lysine methylation regulates the pRb tumour suppressor protein. Oncogene 29, 2357–2367 (2010). https://doi.org/10.1038/onc.2009.511

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