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

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 phos-phatase 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. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Autophagy is regulated by the Beclin 1/Vps34 complex, and the protein phosphatase 6 (PP6) inhibits autophagy by binding to Beclin 1 and causing dissociation of Vps34. The phosphatase activity of PP6 is not involved in this regulatory mechanism.