Cell cycle control and cancer.

This review consists of two parts. In the first part normal mechanisms regulating the progression of cells through the cell cycle are briefly reviewed. Besides mitogenic stimulation, cyclin kinase inhibition, the G1 restriction point and the prb pathway, accuracy of DNA replication and DNA repair, the G2 to M transition, apoptosis and the p 53 pathway, proteolytic, in particular ubiquitin-dependent mechanisms involved in the initiation of DNA synthesis in the separation of sister chromatids and in the telophase to GO/G1 transition, are discussed. In the second part oncogene and tumor suppressor gene products are briefly characterized. Aberrations of cell cycle control mechanisms associated with cancer are grouped as follows: deregulation of protooncogenes by translocations juxtaposing protooncogenes to immunoglobulin--or T cell receptor genes; translocations producing chimeric proteins unique to cancer cells; inversions and amplifications resulting in over expression of regulator genes; and deletions and mutations of tumor suppressor genes. It is emphasized that cancer is the result of a multistep process and that uncontrolled cell production and other alterations are, as a rule, late phenomena.