title: Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth.
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.
authors.affiliation: 1] State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Wen-Dan
authors.initials: WD
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Hai-liang
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Yun-Tian
authors.initials: YT
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Rui-Yan
authors.initials: RY
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Gong-Kan
authors.initials: GK
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhu
mesh_terms: D000107:Acetylation; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D063646:Carcinogenesis; D047389:Casein Kinase I / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism*; D008819:Mice, Nude; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D056564:Sirtuin 1 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D047389:Casein Kinase I; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D056564:Sirtuin 1; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C491997:BECN1 protein, human; C552537:RUBCN protein, human; C447939:SIRT1 protein, human