Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth.

Ting Sun, Xuan Li, Peng Zhang, Wen-Dan Chen, Hai-liang Zhang, Dan-Dan Li, Rong Deng, Xiao-Jun Qian, Lin Jiao, Jiao Ji, Yun-Tian Li, Rui-Yan Wu, Yan Yu, Gong-Kan Feng, Xiao-Feng Zhu

Index: Nat. Commun. 6 , 7215, (2015)

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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.