The p21Cip1 and p27Kip1 CDK ‘inhibitors’ are essential activators of cyclin D dependent kinases in murine fibroblasts. EMBO J

Department of Tumor Cell Biology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
The EMBO Journal (Impact Factor: 10.43). 04/1999; 18(6):1571-83. DOI: 10.1093/emboj/18.6.1571
Source: PubMed


The widely prevailing view that the cyclin-dependent kinase inhibitors (CKIs) are solely negative regulators of cyclin-dependent kinases (CDKs) is challenged here by observations that normal up-regulation of cyclin D- CDK4 in mitogen-stimulated fibroblasts depends redundantly upon p21(Cip1) and p27(Kip1). Primary mouse embryonic fibroblasts that lack genes encoding both p21 and p27 fail to assemble detectable amounts of cyclin D-CDK complexes, express cyclin D proteins at much reduced levels, and are unable to efficiently direct cyclin D proteins to the cell nucleus. Restoration of CKI function reverses all three defects and thereby restores cyclin D activity to normal physiological levels. In the absence of both CKIs, the severe reduction in cyclin D-dependent kinase activity was well tolerated and had no overt effects on the cell cycle.

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    • "Apparently in contrast to its supposed role as cell cycle inhibitor, KRP6 overexpression led to accelerated G1-to-S and G2-to-M transitions in cell cultures. Previously, KRP1 has been found to mediate the transport of CDKA;1 into plant nuclei (Zhou et al., 2006), reminiscent of the situation in mammals, where Cip/Kip proteins have been suggested as assembly and nuclear targeting factors of D-type cyclin complexes to the nucleus (LaBaer et al., 1997; Cheng et al., 1999). In addition, p21 Cip1 promotes nuclear accumulation of CYCD1 by binding to its phosphorylated form to prevent its nuclear export (Alt et al., 2002). "

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    • " M transitions in cell cultures . Previously , KRP1 has been found to mediate the transport of CDKA ; 1 into plant nuclei ( Zhou et al . , 2006 ) , reminiscent of the situation in mammals , where Cip / Kip proteins have been suggested as assembly and nuclear targeting factors of D - type cyclin complexes to the nu - cleus ( LaBaer et al . , 1997 ; Cheng et al . , 1999 ) . In addition , p21 Cip1 promotes nuclear accumulation of CYCD1 by binding to its phosphorylated form to prevent its nuclear export ( Alt et al . , 2002 ) . Analogously , the accelerated G1 - S and G2 - M transition in KRP6 - overexpressing cultures may be explained if KRP6 functions through activation of CDK / CYCD complexes by pro -"
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