Cyclin-dependent regulation of G1 in mammalian fibroblasts.
Eukaryotic cells become committed to proliferate during the G1 phase of the cell cycle. In budding yeast, commitment occurs when the catalytic subunit of a protein kinase, encoded by the CDC28 gene (the homolog of the fission yeast cdc2+ gene), binds to a positively acting regulatory subunit, a cyclin. Related kinases are also required for progression through the G1 phase in higher eukaryotes. The role of cyclins in controlling G1 progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G1, decrease cell size, and diminish the serum requirement for the transition from G1 to S phase. These observations show that cyclin levels can be rate-limiting for G1 progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation.
Ohtsubo
M
M
Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Roberts
J M
JM
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D019868:Kanamycin Kinase; D008297:Male; D010770:Phosphotransferases / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D016196:S Phase / Q000502:physiology; D013997:Time Factors; D014162:Transfection
D016213:Cyclins; D011993:Recombinant Fusion Proteins; D010770:Phosphotransferases; D019868:Kanamycin Kinase