INVESTIGADORES
MUNARRIZ Eliana Rosa
artículos
Título:
PIAS-1 is a checkpoint regulator which affects exit from G1 and G2 by sumoylation of p73.
Autor/es:
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.
Revista:
MOLECULAR AND CELLULAR BIOLOGY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Año: 2004 p. 10593 - 10610
ISSN:
0270-7306
Resumen:
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 p73alpha, -beta, and -gamma bind to the protein inhibitor of
activated STAT-1 (PIAS-1) and that this binding stabilizes p73. PIAS-1
also sumoylates p73alpha, although not the C-terminally truncated
isoforms p73beta and -gamma, and this requires the RING finger domain of
PIAS-1. The DeltaNp73alpha 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 G(1) and cell cycle reentry. Inhibition of
endogenous PIAS-1 by RNA interference reduces the proportion of cells in
S phase and induces G(2) arrest. These data suggest that PIAS-1, acting
partly through binding and sumoylation of p73, is an important
component of the cell cycle machinery.