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Protein phosphatase 6 dissociates the Beclin 1/Vps34 complex and inhibits autophagy
Nobuyuki Fujiwara1, Shusaku Shibutani2, Takashi Ohama3
1Laboratory of Veterinary Pharmacology, 753-8515, Yamaguchi, Japan; Laboratory of Drug Discovery and Pharmacology, Faculty of Veterinary Medicine, Okayama University of Science, 794-8555, Ehime, Japan.
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.
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