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