The SUMO E3-ligase PIAS1 couples reactive oxygen species-dependent JNK activation to oxidative cell death
Leitao, B. B., Jones, M. C. and Brosens, Jan J.. (2011) The SUMO E3-ligase PIAS1 couples reactive oxygen species-dependent JNK activation to oxidative cell death. FASEB Journal, Vol.25 (No.10). pp. 3416-3425. ISSN 0892-6638Full text not available from this repository.
Official URL: http://dx.doi.org/10.1096/fj.11-186346
Human endometrial stromal cells (HESCs) exposed to reactive oxygen species (ROS) mount a hypersumoylation response in a c-Jun N-terminal kinase (JNK)-dependent manner. The mechanism that couples JNK signaling to the small ubiquitin-related modifier (SUMO) pathway and its functional consequences are not understood. We show that ROS-dependent JNK activation converges on the SUMO pathway via PIAS1 (protein inhibitor of activated STAT1). Unexpectedly, PIAS1 knockdown not only prevented ROS-dependent hypersumoylation but also enhanced JNK signaling in HESCs. Conversely, PIAS overexpression increased sumoylation of various substrates, including c-Jun, yet inhibited basal and ROS-dependent JNK activity independently of its SUMO ligase function. Expression profiling demonstrated that PIAS1 knockdown enhances and profoundly modifies the transcriptional response to oxidative stress signals. Using a cutoff of 2-fold change or more, a total of 250 ROS-sensitive genes were identified, 97 of which were not dependent on PIAS1. PIAS1 knockdown abolished the regulation of 43 genes but also sensitized 110 other genes to ROS. Importantly, PIAS1 silencing was obligatory for the induction of several cellular defense genes in response to oxidative stress. In agreement, PIAS1 knockdown attenuated ROS-dependent caspase-3/7 activation and subsequent apoptosis. Thus, PIAS1 determines the level of JNK activity in HESCs, couples ROS signaling to the SUMO pathway, and promotes oxidative cell death.-Leitao, B. B., Jones, M. C., Brosens, J. J. The SUMO E3-ligase PIAS1 couples reactive oxygen species-dependent JNK activation to oxidative cell death.
|Item Type:||Journal Article|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Reproductive Health
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||FASEB Journal|
|Publisher:||Federation of American Societies for Experimental Biology|
|Official Date:||October 2011|
|Page Range:||pp. 3416-3425|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Wellcome Trust (WT), Genesis Trust , UK National Institute for Health Research Biomedical Research Centre|
|Grant number:||084336 (WT)|
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