Mammalian G1 cyclins and cell cycle progression

Since their discovery in 1991, the D- and E-type cyclins, their associated catalytic subunits, and the molecules that regulate their kinase activity have been subjects of intense scrutiny by a rapidly expanding group of investigators. Part of the excitement stems from an emerging realization that these molecules define a final common pathway for growth factor-induced and antiproliferative signals during the cell cycle. As such, their study is helping to describe the biochemical pathways that determine the basis of late GI phase control, much as studies of growth factors, receptors, cytoplasmic signaling molecules, and responding transcription factors helped to define temporally earlier steps in the mitogenic process. In retrospect, it is neither surprising that there is a functional interplay between these cell cycle regulators and previously recognized tumor suppressor gene products (p53 and pRB) that are themselves engaged in GI phase checkpoint control, nor is it surprising that genetic perturbations affecting the functions of these genes contribute to cancer. It seems equally likely that further elucidation of the functions of these molecules will help to better explain such diverse processes as differentiation and apoptosis, which cooperatively depend on the cell cycle machinery for their proper execution.