| Literature DB >> 30711375 |
Ioannis Sanidas1, Robert Morris1, Katerina A Fella1, Purva H Rumde1, Myriam Boukhali1, Eric C Tai1, David T Ting1, Michael S Lawrence2, Wilhelm Haas1, Nicholas J Dyson3.
Abstract
Hyper-phosphorylation of RB controls its interaction with E2F and inhibits its tumor suppressor properties. However, during G1 active RB can be mono-phosphorylated on any one of 14 CDK phosphorylation sites. Here, we used quantitative proteomics to profile protein complexes formed by each mono-phosphorylated RB isoform (mP-RB) and identified the associated transcriptional outputs. The results show that the 14 sites of mono-phosphorylation co-ordinate RB's interactions and confer functional specificity. All 14 mP-RBs interact with E2F/DP proteins, but they provide different shades of E2F regulation. RB mono-phosphorylation at S811, for example, alters RB transcriptional activity by promoting its association with NuRD complexes. The greatest functional differences between mP-RBs are evident beyond the cell cycle machinery. RB mono-phosphorylation at S811 or T826 stimulates the expression of oxidative phosphorylation genes, increasing cellular oxygen consumption. These results indicate that RB activation signals are integrated in a phosphorylation code that determines the diversity of RB activity.Entities:
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Year: 2019 PMID： 30711375 PMCID： PMC6424368 DOI： 10.1016/j.molcel.2019.01.004
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970