Cyclin-Dependent Regulation of G ₁ in Mammalian Fibroblasts

Eukaryotic cells become committed to proliferate during the G 1 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 cdc 2 + gene), binds to a positively acting regulatory subunit, a cyclin. Related kinases are also required for progression through the G 1 phase in higher eukaryotes. The role of cyclins in controlling G 1 progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G 1 , decrease cell size, and diminish the serum requirement for the transition from G 1 to S phase. These observations show that cyclin levels can be rate-limiting for G 1 progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation.