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.
Mesh Terms:
Animals, Cells, Cultured, Gene Knockdown Techniques, Heat-Shock Response, Hela Cells, Humans, Jurkat Cells, Mice, Models, Biological, Poly(ADP-ribose) Polymerases, Protein Inhibitors of Activated STAT, Protein Processing, Post-Translational, SUMO-1 Protein, Spodoptera, Transcriptional Activation, Ubiquitin-Protein Ligases
EMBO J.
Date: Nov. 18, 2009
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