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GENES & DEVELOPMENT 18:2699-2711, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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REVIEW

Living with or without cyclins and cyclin-dependent kinases

Charles J. Sherr1,2,4 and James M. Roberts1,3

1 Howard Hughes Medical Institute and 2 Department of Genetics & Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA; 3 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

Entry into, progression through, and exit from the G1 phase of the mammalian cell cycle in response to extracellular mitogenic cues are presumed to be governed by cyclin-dependent kinases (Cdks) regulated by the D-type and E-type cyclins. Studies performed over more than a decade have supported the view that these holoenzymes are important, if not required, for these processes. However, recent experiments in which the genes encoding all three D-type cyclins, the two E-type cyclins, cyclin D-dependent Cdk4 and Cdk6, or cyclin E-dependent Cdk2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence. Thus, none of these genes is strictly essential for cell cycle progression. To what extent is the prevailing dogma incorrect, and how can the recent findings be reconciled with past work?

[Keywords: Cell cycle; cyclin D; cyclin E; Cdk2; Cdk4; Cdk6]


Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1256504.

4 Corresponding author. E-MAIL sherr{at}stjude.org; FAX (901) 495-2381.


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