MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability.

ABSTRACT: The c-MYC (MYC) oncoprotein is deregulated in over 50% of cancers, yet regulatory mechanisms controlling MYC remain unclear. To this end, we interrogated the MYC interactome using BioID mass spectrometry (MS) and identified PP1 (protein phosphatase 1) and its regulatory subunit PNUTS (protein phosphatase-1 nuclear-targeting subunit) as MYC interactors. We demonstrate that endogenous MYC and PNUTS interact across multiple cell types and that they co-occupy MYC target gene promoters. Inhibiting PP1 by RNAi or pharmacological inhibition results in MYC hyperphosphorylation at multiple serine and threonine residues, leading to a decrease in MYC protein levels due to proteasomal degradation through the canonical SCF^FBXW7 pathway. MYC hyperphosphorylation can be rescued specifically wi

SUBMITTER: Dingar D 

PROVIDER: S-EPMC6115416 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature