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Research Papers
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract
Numerous experiments have defined a critical role for the G1 cyclins and associated kinases in allowing a normal progression of cells from a quiescent state, through G1, and into S phase. We now demonstrate that G1 cyclin-dependent kinase activity is critical for the accumulation of E2F activity late in G1. Moreover, E2F-1 overexpression can overcome a G1 arrest caused by the inhibition of G1 cyclin-dependent kinase activity, consistent with E2F activation being an important consequence of the action of G1 cyclins. E2F-1 also overcomes a G1 block caused by gamma irradiation and leads to an apparent complete replication of the cellular genome and entry into mitosis. This E2F-1-mediated induction of S phase and mitosis is not accompanied by the rise in either cyclin D-associated kinase activity or cdk2 activity that is normally observed during the G1 phase of the cell cycle. We conclude that one key function for G1 cyclin-dependent kinase activity is the activation of E2F-1, that the accumulation of E2F activity may be sufficient to allow initiation and completion of S phase, but that additional events, including G1 cyclin kinase activity, are likely necessary for a normal proliferative event.
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