p53 induces ARTS to promote mitochondrial apoptosis

Abstract A poptosis r elated protein in T GF-? s ignaling pathway (ARTS) was originally discovered cells undergoing apoptosis response to TGF-?, but ARTS also acts downstream of many other apoptotic stimuli. induces by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 variety p53-inducing agents increased both mRNA levels ARTS, whereas ablation reduced expression multiple stress conditions. Also, ?-irradiation induced p53-dependent mice. Consistently, binds responsive DNA element on promoter transcriptionally activated promoter-driven luciferase reporter Interestingly, sequesters at mitochondria, enhancing interaction latter with Bcl-XL. markedly augments damage stress- or Nutlin-3-triggered apoptosis, while preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that collaborates mitochondria-engaged