NDLI: Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity.

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Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity.

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Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Müller, Stefan Schmidt, Darja
Description	Author Affiliation: Schmidt D ( Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18a, D-82152 Martinsried, Germany.);
Abstract	The activity of the p53 tumor suppressor protein and the c-Jun protooncogene is regulated by posttranslational modifications, such as phosphorylation or ubiquitination. In addition, covalent attachment of the ubiquitin-like modifier SUMO appears to modulate their transcriptional activity. Sumoylation proceeds via an enzymatic pathway that is mechanistically analogous to ubiquitination, but requires a different E1-activating enzyme and Ubc9, a SUMO-specific E2-conjugating enzyme. Here, we show that two members of the PIAS family, PIAS1 and PIASxbeta, act as specific E3-like ligases that promote sumoylation of p53 and c-Jun in vitro and in vivo. The PIAS proteins physically interact with both p53 and c-Jun. In addition, they bind to Ubc9, suggesting that they recruit the E2 enzyme to their respective substrate. The SUMO ligase activity requires the conserved zinc-finger domain, which is distantly related to the essential RING-finger motif, found in a subset of ubiquitin ligases. Furthermore, similar to RING-type ubiquitin ligases, PIASxbeta can catalyze its own modification. Hence, these data further extend the analogy between the ubiquitin and SUMO pathway. Strikingly, PIAS proteins strongly repress the transcriptional activity of p53, suggesting that the PIAS-SUMO pathway plays a crucial role in the regulation of p53 and presumably other transcription factors.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Proteins Metabolism Proto-Oncogene Proteins C-jun SUMO-1 Protein Tumor Suppressor Protein P53 Ubiquitin-Conjugating Enzymes Down-Regulation HeLa Cells Ligases Protein Inhibitors Of Activated STAT Genetics Transcriptional Activation Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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