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Originally published In Press as doi:10.1074/jbc.M207497200 on October 28, 2002

J. Biol. Chem., Vol. 278, Issue 2, 1158-1164, January 10, 2003
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The SET Protein Regulates G2/M Transition by Modulating Cyclin B-Cyclin-dependent Kinase 1 Activity*

Núria Canela, Aina Rodriguez-Vilarrupla, Josep María Estanyol, Carmen Díaz, Maria Jesús Pujol, Neus Agell, and Oriol BachsDagger

From the Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi Sunyer, Universitat de Barcelona, Casanova 143, 08036-Barcelona, Spain

The SET protein and the cell cycle inhibitor p21Cip1 interact in vivo and in vitro. We identified here the domain 157LIF159 of p21Cip1 as essential for the binding of SET. We also found that SET contains at least two domains of interaction with p21Cip1, one located in the fragment amino acids 81-180 and the other one in the fragment including amino acids 181-277. SET and p21Cip1 co-localize in the cell nucleus in a temporal manner. Overexpression of SET blocks the cell cycle at the G2/M transition in COS and HCT116 cells. Moreover, SET inhibits cyclin B-CDK1 activity both in vivo and in vitro in both cell types. This effect is specific for these complexes since SET did not inhibit either cyclin A-CDK2 or cyclin E-CDK2 complexes. SET and p21Cip1 cooperate in the inhibition of cyclin B-CDK1 activity. The inhibitory effect of SET resides in its acidic C terminus, as demonstrated by the ability of this domain to inhibit cyclin B-CDK1 activity and by the lack of blocking G2/M transition when a mutated form of SET lacking this C terminus domain was overexpressed in COS cells. These results indicate that SET might regulate G2/M transition by modulating cyclin B-CDK1 activity.


* This work was supported by Ministerio de Educación y Cultura Grants SAF 1999-0028 and SAF 2000-0052).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Cell Biology and Pathology, Faculty of Medicine, University of Barcelona, Casanova 143, 08036-Barcelona, Spain. Tel.: 34-93-403-52-86; Fax: 34-93-402-19-07; E-mail: bachs@medicina.ub.es.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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