PARP-1 transcriptional activity is regulated by sumoylation upon heat shock.
EMBO J
; 28(22): 3534-48, 2009 Nov 18.
Article
em En
| MEDLINE
| ID: mdl-19779455
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
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Poli(ADP-Ribose) Polimerases
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Resposta ao Choque Térmico
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Proteína SUMO-1
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article