REQUIREMENT OF P27(KIP1) FOR RESTRICTION POINT CONTROL OF THE FIBROBLAST CELL-CYCLE

Cells deprived of serum mitogens will either undergo immediate cell cy cle arrest or complete mitosis and arrest in the next cell cycle. The transition from mitogen dependence to mitogen independence occurs in t he mid- to late G(1) phase of the cell cycle and is called the restric tion point. Murine Balb/c-3T3 fibroblasts deprived of serum mitogens a ccumulated the cyclin-dependent kinase (CDK) inhibitor p27(Kip1). This was correlated with inactivation of essential G(1) cyclin-CDK complex es and with cell cycle arrest in G(1). The ability of specific mitogen s to allow transit through the restriction point paralleled their abil ity to down-regulate p27, and antisense inhibition of p27 expression p revented cell cycle arrest in response to mitogen depletion. Therefore , p27 is an essential component of the pathway that connects mitogenic signals to the cell cycle at the restriction point.