Author/Authors :
Caroline H. Yi، نويسنده , , Heling Pan، نويسنده , , Jan Seebacher، نويسنده , , Il-Ho Jang، نويسنده , , Sven G. Hyberts، نويسنده , , Gregory J. Heffron، نويسنده , , Matthew G. Vander Heiden، نويسنده , , Renliang Yang، نويسنده , , Fupeng Li، نويسنده , , Jason W. Locasale، نويسنده , , Hadar Sharfi، نويسنده , , Bo Zhai، نويسنده , , Ricard Rodriguez-Mias، نويسنده , , Harry Luithardt، نويسنده , , Lewis C. Cantley، نويسنده , , George Q. Daley، نويسنده , , John M. Asara، نويسنده , , Steven P. Gygi، نويسنده , , Gerhard Wagner، نويسنده , , Chuan-Fa Liu، نويسنده , , et al.، نويسنده ,
Abstract :
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 acetyl-CoA. 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.
