Nitric Oxide Destabilizes Pias3 and Regulates Sumoylation
Open Access
- 31 October 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 2 (10), e1085
- https://doi.org/10.1371/journal.pone.0001085
Abstract
Small ubiquitin-related protein modifiers (SUMO) modification is an important mechanism for posttranslational regulation of protein function. However, it is largely unknown how the sumoylation pathway is regulated. Here, we report that nitric oxide (NO) causes global hyposumoylation in mammalian cells. Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3) were targets for S-nitrosation. S-nitrosation did not interfere with the SUMO conjugating activity of Ubc9, but promoted Pias3 degradation by facilitating its interaction with tripartite motif-containing 32 (Trim32), a ubiquitin E3 ligase. On the one hand, NO promoted Trim32-mediated Pias3 ubiquitination. On the other hand, NO enhanced the stimulatory effect of Pias3 on Trim32 autoubiquitination. The residue Cys459 of Pias3 was identified as a target site for S-nitrosation. Mutation of Cys459 abolished the stimulatory effect of NO on the Pias3-Trim32 interaction, indicating a requirement of S-nitrosation at Cys459 for positive regulation of the Pias3-Trim32 interplay. This study reveals a novel crosstalk between S-nitrosation, ubiquitination, and sumoylation, which may be crucial for NO-related physiological and pathological processes.Keywords
This publication has 31 references indexed in Scilit:
- PIAS3 Interacts with ATF1 and Regulates the Human Ferritin H Gene through an Antioxidant-responsive ElementPublished by Elsevier BV ,2007
- Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of Cysteines 93 and 310Nucleic Acids Research, 2007
- Ubc9 fusion–directed SUMOylation (UFDS): a method to analyze function of protein SUMOylationNature Methods, 2007
- Regulation of the SUMO pathway sensitizes differentiating human endometrial stromal cells to progesteroneProceedings of the National Academy of Sciences of the United States of America, 2006
- Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteinsThe EMBO Journal, 2006
- PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleusNucleic Acids Research, 2006
- Identification of S-nitrosylation motifs by site-specific mapping of the S -nitrosocysteine proteome in human vascular smooth muscle cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- Trim32 is a Ubiquitin Ligase Mutated in Limb Girdle Muscular Dystrophy Type 2H that Binds to Skeletal Muscle Myosin and Ubiquitinates ActinJournal of Molecular Biology, 2005
- PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger proteinExperimental Cell Research, 2005
- The Polycomb Protein Pc2 Is a SUMO E3Cell, 2003