PARP-1 transcriptional activity is regulated by sumoylation upon heat shock.
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.
Department of Cell Biology and Infection, Nuclear Organisation and Oncogenesis Unit, INSERM U579, Institut Pasteur, Paris, France.
Nadine
N
Martin
Klaus
K
Schwamborn
Valérie
V
Schreiber
Andreas
A
Werner
Christelle
C
Guillier
Xiang-Dong
XD
Zhang
Oliver
O
Bischof
Jacob-S
JS
Seeler
Anne
A
Dejean
D000818:Animals; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008954:Models, Biological; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism* / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D025842:SUMO-1 Protein / Q000378:metabolism*; D018411:Spodoptera; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology
C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D044767:Ubiquitin-Protein Ligases; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases