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

MUNARRIZ E, BARCAROLI D, STEPHANOU A, TOWNSEND PA, MAISSE C, TERRINONI A, NEALE MH, MARTIN SJ, LATCHMAN DS, KNIGHT RA, MELINO G, DE LAURENZI V.

Siena

Conferencia; 3rd Tuscany Retreat on: ”Cancer: from its birth to its death".; 2003

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 p73, -, and - bind to the protein inhibitor of activated STAT-1 (PIAS-1) and that this binding stabilizes p73. PIAS-1 also sumoylates p73, although not the C-terminally truncated isoforms p73 and -, and this requires the RING finger domain of PIAS-1. The Np73 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.