Regulation of the Proapoptotic ARTS Protein by Ubiquitin-mediated Degradation

Rona Lotan, Asaf Rotem, Hedva Gonen, John P. M. Finberg, Stav Kemeny, Hermann Steller, Aaron Ciechanover, Sarit Larisch
2005 Journal of Biological Chemistry  
ARTS is a mitochondrial protein that promotes apoptosis induced by a variety of proapoptotic stimulators. ARTS induces apoptosis, at least in part, through binding to and antagonizing IAPs (inhibitors of apoptosis proteins). As a result of ARTS binding to IAPs, caspase inhibition is removed and apoptosis can be executed. Here we show that high cellular levels of ARTS protein sensitize cells toward apoptosis. Accordingly, in healthy cells ARTS levels are kept low through constant
more » ... ant ubiquitin-mediated degradation. Upon proapoptotic stimuli, the ubiquitination process is inhibited, resulting in increased levels of ARTS. Increased ARTS in turn leads to a decrease of Bcl-2 and Bcl-x L protein levels, cytochrome c release from mitochondria and apoptosis.
doi:10.1074/jbc.m501955200 pmid:15837787 fatcat:ijygbqy2xvc3lapnycqtngw5yq