Protein phosphatase 6 dissociates the Beclin 1/Vps34 complex and inhibits autophagy

Biochem Biophys Res Commun. 2021 May 7:552:191-195. doi: 10.1016/j.bbrc.2021.02.136. Epub 2021 Mar 20.

Abstract

Autophagy is an evolutionarily conserved intracellular degradation system and is regulated by various signaling pathways including the Beclin 1/Vacuolar protein sorting 34 (Vps34) complex. Protein phosphatase 6 (PP6) is an essential serine/threonine phosphatase that regulates various biological processes. Recently, we found that PP6 protein is degraded by p62-dependent selective autophagy. In this study, we show that PP6 conversely inhibits autophagy. PP6 associate with the C-terminal region of Beclin 1, which is close to the binding region of Vps34. The protein levels of PP6 affect Beclin 1/Vps34 complex formation and phosphatase activity of PP6 is not involved in this. We also show that chemically induced PP6/Beclin 1 association leads to Vps34 dissociation from Beclin 1. Overall, our data reveal a novel regulatory mechanism for autophagy by PP6.

Keywords: Autophagy; Beclin 1; Protein-protein interaction; Serine/threonine protein phosphatase 6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Beclin-1 / metabolism*
  • Cells, Cultured
  • Class III Phosphatidylinositol 3-Kinases / metabolism*
  • Embryo, Mammalian / cytology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Multiprotein Complexes / metabolism
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*

Substances

  • Beclin-1
  • Multiprotein Complexes
  • Class III Phosphatidylinositol 3-Kinases
  • Phosphoprotein Phosphatases
  • protein phosphatase 6