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Mol Cell Biol, June 1998, p. 3163-3172, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Increased Expression of Cyclin D2 during Multiple
States of Growth Arrest in Primary and Established Cells
Muthupalaniappan
Meyyappan,1
Howard
Wong,2
Christopher
Hull,3 and
Karl T.
Riabowol3,4,*
Departments of Medical
Science,1
Medical
Biochemistry,3 and
Oncology,4 Southern Alberta Cancer
Research Center, and
Department of Molecular Pathology,
University of Calgary Health Sciences Center,2
Calgary, Alberta, Canada T2N 4N1
Received 10 December 1997/Accepted 18 February 1998
Cyclin D2 is a member of the family of D-type cyclins that is
implicated in cell cycle regulation, differentiation, and oncogenic transformation. To better understand the role of this cyclin in the
control of cell proliferation, cyclin D2 expression was monitored under
various growth conditions in primary human and established murine
fibroblasts. In different states of cellular growth arrest initiated by
contact inhibition, serum starvation, or cellular senescence, marked
increases (5- to 20-fold) were seen in the expression levels of cyclin
D2 mRNA and protein. Indirect immunofluorescence studies showed that
cyclin D2 protein localized to the nucleus in G0,
suggesting a nuclear function for cyclin D2 in quiescent cells. Cyclin
D2 was also found to be associated with the cyclin-dependent kinases
CDK2 and CDK4 but not CDK6 during growth arrest. Cyclin D2-CDK2
complexes increased in amounts but were inactive as histone H1 kinases
in quiescent cells. Transient transfection and needle microinjection of
cyclin D2 expression constructs demonstrated that overexpression of
cyclin D2 protein efficiently inhibited cell cycle progression and DNA
synthesis. These data suggest that in addition to a role in promoting
cell cycle progression through phosphorylation of retinoblastoma family
proteins in some cell systems, cyclin D2 may contribute to the
induction and/or maintenance of a nonproliferative state, possibly
through sequestration of the CDK2 catalytic subunit.
*
Corresponding author. Mailing address: Department of
Medical Biochemistry, University of Calgary Health Sciences Center,
3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1. Phone: (403) 220-8695. Fax: (403) 270-0834. E-mail:
kriabowo{at}acs.ucalgary.ca.
Mol Cell Biol, June 1998, p. 3163-3172, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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