Cyclins and cell cycle checkpoints

The eucaryotic cell cycle is regulated by the periodic synthesis and destru ction of cyclins that associate with and activate cyclin-dependent kinases. Cyclin-dependent kinase inhibitors, such as p21 and p16, also play importa nt roles in cell cycle control by coordinating internal and external signal s and impeding proliferation at several key checkpoints. Understanding how these proteins interact to regulate the cell cycle has become increasingly important to researchers and clinicians with the discovery that many of the genes that encode cell cycle regulatory activities are targets for alterat ions that underlie the development of cancer. Several therapeutic agents, s uch as DNA-damaging drugs, microtubule inhibitors, antimetabolites, and top oisomerase inhibitors, take advantage of this disruption in normal cell cyc le regulation to target checkpoint controls and ultimately induce growth ar rest or apoptosis of neoplastic cells. Other therapeutic drugs being develo ped, such as UCN-01, specifically inhibit cell cycle regulatory proteins.