IBIOBA - MPSP 22718
INSTITUTO DE INVESTIGACION EN BIOMEDICINA DE BUENOS AIRES - INSTITUTO PARTNER DE LA SOCIEDAD MAX PLANCK
Unidad Ejecutora - UE
artículos
Título:
CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
Autor/es:
TAREK ABBAS; ADAM C. MUELLER; ETSUKO SHIBATA; MIGNON KEATON; MARIO ROSSI; ANINDYA DUTTA
Revista:
MOLECULAR CELL
Editorial:
CELL PRESS
Referencias:
Lugar: United States; Año: 2013 vol. 49 p. 1147 - 1158
ISSN:
1097-2765
Resumen:
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The Cul4-Cdt2 (CRL4Cdt2) E3 ubiquitin ligase is a master regulator of
cell-cycle progression and genome stability. Despite its central role in the
degradation of many cell-cycle regulators, e.g., Cdt1, p21, and Pr-Set7/Set8,
little is known about the regulation of its activity. We report that Cdt2 is
autoubiquitylated by the CRL4A E3 ubiquitin ligase. Cdt2 is additionally
polyubiquitylated and degraded by Cul1-FBXO11 (CRL1FBXO11). CRL1FBXO11-mediated degradation of Cdt2 stabilizes p21 and Set8, and this is
important during the response to TGF-b, with the Set8 induction being important
for turning off the activation of Smad2. The migration of epithelial cells is
also stimulated by CRL1FBXO11-mediated downregulation
of Cdt2 and the consequent stabilization of Set8. This is an interesting
example of crossregulation between specific Cullin 4 and Cullin 1 E3 ubiquitin
ligases and highlights the role of ubiquitylation in regulating cellular
responses to TGF-b and the migration of epithelial cells.
