PIASy-mediated Tip60 sumoylation regulates p53-induced autophagy

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...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2012-07, Vol.11 (14), p.2717-2728
Main Authors: Naidu, Samisubbu R., Lakhter, Alexander J., Androphy, Elliot J.
Format: Article
Language:English
Subjects:
Acetylation
Apoptosis
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Autophagy
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Line
Cycle
HCT116 Cells
Histone Acetyltransferases - metabolism
Humans
Landes
Lysine Acetyltransferase 5
Mutation
Organogenesis
PIASy
Poly-ADP-Ribose Binding Proteins
Protein Binding
Protein Inhibitors of Activated STAT - metabolism
Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Sumoylation
sumoylation and tumor suppressors
Tip60
Tumor Suppressor Protein p14ARF - metabolism
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.21091