HUMAN CPR (CELL-CYCLE PROGRESSION RESTORATION) GENES IMPART A FAR(-) PHENOTYPE ON YEAST-CELLS

Regulated cell cycle progression depends on the proper integration of growth control pathways with the basic cell cycle machinery. While man y of the central molecules such as cyclins, CDKs, and CKIs are known, and many of the kinases and phosphatases that modify the CDKs hare bee n identified, little is known about the additional layers of regulatio n that impinge upon these molecules. To identify new regulators of cel l proliferation, we have selected for human and yeast cDNAs that when overexpressed were capable of specifically overcoming G(1) arrest sign als from the cell cycle branch of the mating pheromone pathway, while still maintaining the integrity of the transcriptional induction branc h. We have identified 13 human CPR (cell cycle progression restoration ) genes and 11 yeast OPY (overproduction-induced pheromone-resistant y east) genes that specifically block the G(1) arrest by mating pheromon e. The CPR genes represent a variety of biochemical functions includin g a new cyclin, a tumor suppressor binding protein, chaperones, transc ription factors, translation factors, RNA-binding proteins, as well as novel proteins. Several CPR genes require individual CLNs to promote pheromone resistance and those that require CLN3 increase the basal le vels of Cln3 protein. Moreover, several of the yeast OPY genes have ov erlapping functions with the human CPR genes, indicating a possible co nservation of roles.