p21-containing cyclin kinases exist in both active and inactive states.
In normal fibroblasts CDKs exist predominantly in p21/PCNA/cyclin/CDK quaternary complexes, whereas in p53-deficient cells, p21 expression is depressed and the kinases are reduced to a cyclin/CDK binary state. p21 is a universal cyclin kinase inhibitor, but we show here that p21-containing complexes exist in both catalytically active and inactive forms. This finding challenges the current view that active cyclin kinases function only in the binary state and reveals the subtlety with which tumor-suppressor proteins modulate the cell cycle.
Zhang
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H
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Hannon
G J
GJ
Beach
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D
D001483:Base Sequence; D002384:Catalysis; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry* / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018809:Proliferating Cell Nuclear Antigen; D018844:Cyclin-Dependent Kinases; D016283:Proto-Oncogene Proteins p21(ras)