Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival

被引：166

作者：

Yi, Caroline H. ^{[1
]}

Pan, Heling ^{[1
]}

Seebacher, Jan ^{[1
]}

Jang, Il-Ho ^{[4
]}

Hyberts, Sven G. ^{[2
]}

Heffron, Gregory J. ^{[2
]}

Vander Heiden, Matthew G. ^{[3
,7
,8
]}

Yang, Renliang ^{[9
]}

Li, Fupeng ^{[9
]}

Locasale, Jason W. ^{[3
]}

Sharfi, Hadar ^{[3
]}

Zhai, Bo ^{[1
]}

Rodriguez-Mias, Ricard ^{[2
]}

Luithardt, Harry ^{[10
]}

Cantley, Lewis C. ^{[3
,5
,6
]}

Daley, George Q. ^{[4
]}

Asara, John M. ^{[5
,6
]}

Gygi, Steven P. ^{[1
]}

Wagner, Gerhard ^{[2
]}

Liu, Chuan-Fa ^{[9
]}

Yuan, Junying ^{[1
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Dept Cell Biol, Boston, MA 02115 USA

[2] Beth Israel Deaconess Med Ctr, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[3] Beth Israel Deaconess Med Ctr, Dept Syst Biol, Boston, MA 02115 USA

[4] Beth Israel Deaconess Med Ctr, Childrens Hosp Boston, Boston, MA 02115 USA

[5] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[8] MIT, Koch Inst, Cambridge, MA 02142 USA

[9] Nanyang Technol Univ, Sch Biol Sci, Div Chem Biol & Biotechnol, Singapore 637551, Singapore

[10] Solut Labs, Cambridge, MA 02139 USA

来源：

CELL | 2011年 / 146卷 / 04期

基金：

美国国家卫生研究院;

关键词：

BCL-X(L) PREVENTS; APOPTOSIS; DEATH; CYCLE; (-)-HYDROXYCITRATE; ACCUMULATION; SUBTILISIN; CLONING; SWITCH; YEAST;

D O I：

10.1016/j.cell.2011.06.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Previous experiments suggest a connection between the N-alpha-acetylation of proteins and sensitivity of cells to apoptotic signals. Here, we describe a biochemical assay to detect the acetylation status of proteins and demonstrate that protein N-alpha-acetylation is regulated by the availability of acetylCoA. Because the antiapoptotic protein Bcl-xL is known to influence mitochondrial metabolism, we reasoned that Bcl-xL may provide a link between protein N-alpha-acetylation and apoptosis. Indeed, Bcl-xL overexpression leads to a reduction in levels of acetyl-CoA and N-alpha-acetylated proteins in the cell. This effect is independent of Bax and Bak, the known binding partners of Bcl-xL. Increasing cellular levels of acetyl-CoA by addition of acetate or citrate restores protein N-alpha-acetylation in Bcl-xL-expressing cells and confers sensitivity to apoptotic stimuli. We propose that acetyl-CoA serves as a signaling molecule that couples apoptotic sensitivity to metabolism by regulating protein N-alpha-acetylation.

引用

页码：607 / 620

页数：14

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