Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3)

J Biol Chem. 2016 May 13;291(20):10858-66. doi: 10.1074/jbc.M115.704908. Epub 2016 Mar 18.


Autophagy is an evolutionarily conserved intracellular degradation system that is involved in cell survival and activated in various diseases, including cancer. Beclin 1 is a central scaffold protein that assembles components for promoting or inhibiting autophagy. Association of Beclin 1 with its interacting proteins is regulated by the phosphorylation of Beclin 1 by various Ser/Thr kinases, but the Ser/Thr phosphatases that regulate these phosphorylation events remain unknown. Here we identify Ser-90 in Beclin 1 as a regulatory site whose phosphorylation is markedly enhanced in cells treated with okadaic acid, an inhibitor of protein phosphatase 2A (PP2A). Beclin 1 Ser-90 phosphorylation is induced in skeletal muscle tissues isolated from starved mice. The Beclin 1 S90A mutant blocked starvation-induced autophagy. We found association of PP2A B55α with Beclin 1, which dissociate by starvation. We also found that death-associated protein kinase 3 directly phosphorylates Beclin 1 Ser-90. We propose that physiological regulation of Beclin 1 Ser-90 phosphorylation by PP2A and death-associated protein kinase 3 controls autophagy.

Keywords: Beclin 1 (BECN1); autophagy; phosphatase; protein phosphatase 2 (PP2A); protein serine/threonine phosphatase (PSP).

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Death-Associated Protein Kinases / metabolism
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphorylation
  • Protein Phosphatase 2 / antagonists & inhibitors*


  • Okadaic Acid
  • Death-Associated Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2