title: The SUMO ligase PIAS1 regulates UV-induced apoptosis by recruiting Daxx to SUMOylated foci.
abstract: The small ubiquitin-like modifier (SUMO) ligase PIAS1 (Protein Inhibitor of Activated Stat-1) has been shown to play a role in cellular stress response by SUMOylating several proteins that are involved in DNA repair, apoptosis and transcription. In this paper, we show that PIAS1 regulates ultraviolet (UV)-induced apoptosis by recruiting Death-associated protein 6 (Daxx) to PIAS1-generated SUMO-foci. Cells that ectopically express PIAS1, but not other PIASes, show increased sensitivity to UV irradiation, suggesting that PIAS1 has a distinct function in UV-dependent apoptosis. Domain analysis of PIAS1 indicates that both PIAS1 SUMO-ligase activity and the specific localization of PIAS1 through its N-terminal and C-terminal domains are essential for UV-induced cell death. Daxx colocalizes with PIAS1-generated SUMOylated foci, and the reduction of Daxx using RNAi alleviates UV-induced apoptosis in PIAS1-expressing cells. PIAS1-mediated recruitment of Daxx and apoptosis following UV irradiation are dependent upon the Daxx C-terminal SUMO-interacting motif (SIM). Overall, our data suggest that the pro-apoptotic protein Daxx specifically interacts with one or more substrates SUMOylated by PIAS1 and this interaction leads to apoptosis following UV irradiation.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Haworth Hall, Rm. 3037, Lawrence, KS 66045,  USA.
authors.forename: Raghavi
authors.initials: R
authors.lastname: Sudharsan
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Azuma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D056970:Co-Repressor Proteins; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000528:radiation effects; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation / Q000235:genetics / Q000502:physiology; D014466:Ultraviolet Rays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D025841:Small Ubiquitin-Related Modifier Proteins