title: PIASy-mediated Tip60 sumoylation regulates p53-induced autophagy.
abstract: Posttranslational modifications of p53 integrate diverse stress signals and regulate its activity, but their combinatorial contribution to overall p53 function is not clear. We investigated the roles of lysine (K) acetylation and sumoylation on p53 and their relation to apoptosis and autophagy. Here we describe the collaborative role of the SUMO E3 ligase PIASy and the lysine acetyltransferase Tip60 in p53-mediated autophagy. PIASy binding to p53 and PIASy-activated Tip60 lead to K386 sumoylation and K120 acetylation of p53, respectively. Even though these two modifications are not dependent on each other, together they act as a "binary death signal" to promote cytoplasmic accumulation of p53 and execution of PUMA-independent autophagy. PIASy-induced Tip60 sumoylation augments p53 K120 acetylation and apoptosis. In addition to p14(ARF) inactivation, impairment in this intricate signaling may explain why p53 mutations are not found in nearly 50% of malignancies.
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA. naidus@iupui.edu
authors: Samisubbu R
authors: SR
authors: Naidu
authors: Alexander J
authors: AJ
authors: Lakhter
authors: Elliot J
authors: EJ
authors: Androphy
mesh_terms: D000107:Acetylation; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D002460:Cell Line; D045325:HCT116 Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D011518:Proto-Oncogene Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5