PIAS-1 is a checkpoint regulator which affects exit from G1 and G2 by sumoylation of p73

Eliana Munarriz, Daniela Barcaroli, Anastasis Stephanou, Paul A. Townsend, Carine Maisse, Alessandro Terrinoni, Michael H. Neale, Seamus J. Martin, David S. Latchman, Richard A. Knight, Gerry Melino, Vincenzo De Laurenzi

Research output: Contribution to journalArticlepeer-review

Abstract

p73 is a recently described member of the p53 family, and, like p53, it undergoes a number of posttranslational modifications. Here we show, by yeast two-hybrid screening, pull-down assays, and coimmunoprecipitation, that p73α, -β, and -γ bind to the protein inhibitor of activated STAT-1 (PIAS-1) and that this binding stabilizes p73. PIAS-1 also sumoylates p73α, although not the C-terminally truncated isoforms p73β and -γ, and this requires the RING finger domain of PIAS-1. The ΔNp73α isoform can also bind, and be sumoylated by, PIAS-1. PIAS-1-mediated sumoylation decreases p73 transcriptional activity on several target promoters, such as Bax. p73 is colocalized in the nucleus with PIAS-1, and sumoylated p73 is located exclusively in the nuclear matrix. PIAS-1 is expressed predominantly during S phase, and PIAS-1 overexpression reduces p73-mediated transcription of p21, with a reduction of cells in G1 and cell cycle reentry. Inhibition of endogenous PIAS-1 by RNA interference reduces the proportion of cells in S phase and induces G2 arrest. These data suggest that PIAS-1, acting partly through binding and sumoylation of p73, is an important component of the cell cycle machinery.

Original languageEnglish
Pages (from-to)10593-10610
Number of pages18
JournalMolecular and Cellular Biology
Volume24
Issue number24
DOIs
Publication statusPublished - Dec 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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