PARP-1 transcriptional activity is regulated by sumoylation upon heat shock

• Published in: The EMBO journal Vol. 28; no. 22; pp. 3534 - 3548
• Main Authors: Martin, Nadine, Schwamborn, Klaus, Schreiber, Valérie, Werner, Andreas, Guillier, Christelle, Zhang, Xiang-Dong, Bischof, Oliver, Seeler, Jacob-S, Dejean, Anne
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 18.11.2009; Nature Publishing Group UK; Springer Nature B.V; EMBO Press; Nature Publishing Group
• Subjects: Animals; Cells, Cultured; Cellular Biology; Chromatin; EMBO09; EMBO31; Environmental stress; Gene expression; Gene Knockdown Techniques; heat shock; Heat-Shock Response - physiology; HeLa Cells; Humans; Jurkat Cells; Kinetics; Life Sciences; Mice; Models, Biological; Molecular biology; PARP-1; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - metabolism; Poly(ADP-ribose) Polymerases - physiology; Poly-ADP-Ribose Binding Proteins; Protein Inhibitors of Activated STAT - metabolism; Protein Inhibitors of Activated STAT - physiology; Protein Processing, Post-Translational - physiology; Spodoptera; SUMO; SUMO-1 Protein - metabolism; Transcriptional Activation; Ubiquitin-Protein Ligases - metabolism; Ubiquitin-Protein Ligases - physiology; PARP‐1; heat shock; SUMO; PARP-1; HEAT SHOCK
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/emboj.2009.279

Heat shock and other environmental stresses rapidly induce transcriptional responses subject to regulation by a variety of post‐translational modifications. Among these, poly(ADP‐ribosyl)ation and sumoylation have received growing attention. Here we show that the SUMO E3 ligase PIASy interacts with the poly(ADP‐ribose) polymerase PARP‐1, and that PIASy mediates heat shock‐induced poly‐sumoylation of PARP‐1. Furthermore, PIASy, and hence sumoylation, appears indispensable for full activation of the inducible HSP70.1 gene. Chromatin immunoprecipitation experiments show that PIASy, SUMO and the SUMO‐conjugating enzyme Ubc9 are rapidly recruited to the HSP70.1 promoter upon heat shock, and that they are subsequently released with kinetics similar to PARP‐1. Finally, we provide evidence that the SUMO‐targeted ubiquitin ligase RNF4 mediates heat‐shock‐inducible ubiquitination of PARP‐1, regulates the stability of PARP‐1, and, like PIASy, is a positive regulator of HSP70.1 gene activity. These results, thus, point to a novel mechanism for regulating PARP‐1 transcription function, and suggest crosstalk between sumoylation and RNF4‐mediated ubiquitination in regulating gene expression in response to heat shock.