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

Nadine Martin, Klaus Schwamborn, Valérie Schreiber, Andreas Werner, Christelle Guillier, Xiang‐Dong Zhang, Oliver Bischof, Jacob‐S Seeler, Anne Dejean

Author Affiliations

  1. Nadine Martin1,,
  2. Klaus Schwamborn1,,
  3. Valérie Schreiber2,,
  4. Andreas Werner1,§,
  5. Christelle Guillier3,||,
  6. Xiang‐Dong Zhang4,
  7. Oliver Bischof1,
  8. Jacob‐S Seeler*,1 and
  9. Anne Dejean*,1
  1. 1 Department of Cell Biology and Infection, Nuclear Organisation and Oncogenesis Unit, INSERM U579, Institut Pasteur, Paris, France
  2. 2 IREBS‐FRE3211, CNRS, Université de Strasbourg, ESBS, Illkirch, France
  3. 3 Plate‐forme protéomique, Institut de Biologie Moléculaire et Cellulaire, CNRS, Strasbourg, France
  4. 4 Department of Biochemistry and Molecular Biology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA
  1. *Corresponding authors. BCI‐ONO‐INSERM U579, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris Cedex 15, France. Tel.: +33 45 6880 86; Fax: +33 145 6889 43; E-mail: jacob.seeler{at}pasteur.fr or Tel.: +33 145 6888 86; Fax: +33 145 6889 43; E-mail: anne.dejean{at}pasteur.fr
  1. These authors contributed equally to this work

  • Present address: Cell Proliferation Group, MRC Clinical Sciences Centre, London W120NN, UK

  • Present address: Pepscan Therapeutics BV, Lelystad 8219 PK, The Netherlands

  • § Present address: ZMBH, University Heidelberg, Heidelberg 69120, Germany

  • || Present address: UMR INRA/CNRS, Université de Bourgogne, Dijon 21 065, France

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Abstract

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.

  • Received March 13, 2009.
  • Accepted August 27, 2009.
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