Identification of PPM1D as an essential Ulk1 phosphatase for genotoxic stress-induced autophagy.

ABSTRACT: Autophagy is an evolutionary conserved process that degrades subcellular constituents. Unlike starvation-induced autophagy, the molecular mechanism of genotoxic stress-induced autophagy has not yet been fully elucidated. In this study, we analyze the molecular mechanism of genotoxic stress-induced autophagy and identify an essential role of dephosphorylation of the Unc51-like kinase 1 (Ulk1) at Ser⁶³⁷, which is catalyzed by the protein phosphatase 1D magnesium-dependent delta isoform (PPM1D). We show that after exposure to genotoxic stress, PPM1D interacts with and dephosphorylates Ulk1 at Ser⁶³⁷ in a p53-dependent manner. The PPM1D-dependent Ulk1 dephosphorylation triggers Ulk1 puncta formation and induces autophagy. This happens not only in mouse embryonic fibroblas

SUBMITTER: Torii S 

PROVIDER: S-EPMC5090708 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature