Regulation of cyclin E and p27kip during mitosis in BALB/c 3T3 cells

We have examined the level of cyclin E, a G1 cyclin, and p27kip, a cyclin-dependent kinase inhibitor, in BALB/c 3T3 cells. Cell populations stimulated to undergo cell cycle traverse displayed little change in the level of cyclin E, while p27kip was found to be reduced 50-80% in proliferating cells. Analysis of mitotic cells, however, revealed that cyclin E is virtually absent and begins to reaccumulate soon after mitosis is complete, as does p27kip. Immunoprecipitation experiments revealed that p27kip is associated with cyclin E in quiescent but not proliferating cells, indicating that it may function to prevent development of cyclin E activity in the absence of growth factors. Based on our characterization of cyclin E and p27kip in BALB/c 3T3 cells during progression of the cell cycle, we propose a model of growth regulation controlling the G1 phase of growing and quiescent cells involving mitotic degradation of cyclin E and recovery of p27kip inhibitory activity in a late or postmitotic interval.