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Lysine methylation regulates the pRb tumour suppressor protein | Oncogene
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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.
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nature portfolio permissions reprints privacy policy retinoblastoma tumour-suppressor protein advertising social media author information authors retinoblastoma tumour suppressor nature 352 nature 432 nature 359 nature 425 nature 412 nature 419 nature 358 nature author correspondence mef2-dependent gene expression dna-damage-responsive acetylation personal data springerlink instant access supplementary figures 1i lysine methylation regulates data protection heterochromatin protein hp1 set7 lysine methyltransferase permissions position-dependent transcriptional regulation e2f transactivation domain murine development methylated prb interacts rb lxcxe-binding function retinoblastoma protein acts van der valk cell-cycle arrest retinoblastoma gene product prb controls proliferation supplementary figure legend retinoblastoma protein switches retinoblastoma gene family cell cycle progression privacy human tumor xenografts histone methyltransferase set7/9 cell cycle control central role c-terminal region issue learn c-terminal truncation set9-mediated methylation
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