Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth

Nat Commun. 2015 May 26;6:7215. doi: 10.1038/ncomms8215.

Abstract

Beclin 1, a protein essential for autophagy, regulates autophagy by interacting with Vps34 and other cofactors to form the Beclin 1 complex. Modifications of Beclin 1 may lead to the induction, inhibition or fine-tuning of the autophagic response under a variety of conditions. Here we show that Beclin 1 is acetylated by p300 and deacetylated by SIRT1 at lysine residues 430 and 437. In addition, the phosphorylation of Beclin 1 at S409 by CK1 is required for the subsequent p300 binding and Beclin 1 acetylation. Beclin 1 acetylation inhibits autophagosome maturation and endocytic trafficking by promoting the recruitment of Rubicon. In tumour xenografts, the expression of 2KR mutant Beclin 1 (substitution of K430 and K437 to arginines) leads to enhanced autophagosome maturation and tumour growth suppression. Therefore, our study identifies an acetylation-dependent regulatory mechanism governing Beclin 1 function in autophagosome maturation and tumour growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Autophagy-Related Proteins
  • Beclin-1
  • Carcinogenesis*
  • Casein Kinase I / metabolism
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MCF-7 Cells
  • Membrane Proteins / metabolism*
  • Mice, Nude
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Sirtuin 1 / metabolism
  • p300-CBP Transcription Factors / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Autophagy-Related Proteins
  • BECN1 protein, human
  • Beclin-1
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RUBCN protein, human
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Casein Kinase I
  • SIRT1 protein, human
  • Sirtuin 1