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Cell Cycle, Cell Death and Senescence

Expression of Cyclin-Dependent Kinase 6, but not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse Astrocytes¹

Department of Biology, Connecticut College, New London, CT

Requests for reprints: Martha J. Grossel, Department of Biology, Box 5331, Connecticut College, 270 Mohegan Ave., New London, CT 06320. Phone: (860) 439-5209; Fax: (860) 439-2519. E-mail: mjgro{at}conncoll.edu

Disruption of the pRb pathway is a common mechanism in tumor formation. The D-cyclin-associated kinases, cyclin-dependent kinase (cdk) 4 and cdk6, are important regulators of the G₁-S phase transition and are elevated in several types of cancers, including gliomas. To investigate potential functional differences in these kinases, mouse astrocytes were taken from chimeric mice and propagated in tissue culture. These multipolar tissue-culture astrocytes were infected with viruses expressing either cdk4 or cdk6. Interestingly, expression of cdk6 resulted in a distinct and rapid morphology change from multipolar to bipolar. This change was not observed in control astrocytes or in astroyctes infected with cdk4. Several other differences in cdk4- and cdk6-infected cells were noted, including differential binding to a subset of cell-cycle inhibitor proteins and a distinct pattern of subcellular localization of these kinases. Immunoblot and immunofluorescence analyses revealed that cdk6-infected astrocytes had an altered expression profile of known markers of glial differentiation. Together, these data indicate several important differences between cdk4 and cdk6 that highlight unique functional roles for these cyclin-dependent kinases.

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