Mammalian antiproliferative signals and their targets.

The effect of mitogens on the mammalian cell cycle is opposed by the action of antimitogens, such as TGF-beta, cAMP agonists, and various antiproliferative drugs. The recent identification of TGF-beta receptors that initiate antimitogenic signals and of cell cycle kinase inhibitors that respond to these signals has provided new insights into this process. The evidence argues that mitogenic and antimitogenic signals confront each other by regulating in opposite ways the activity of cyclin-dependent kinases that control cell commitment to DNA replication.