TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation

PTEN/MMAC1/TEP1 (PTEN, phosphatase deleted on chromosome ten; MMAC1, mutate d in multiple advanced cancers; TEP1, tensin-like phosphatase) is a major h uman tumor suppressor gene whose suppressive activity operates on the phosp hatidylinositol pathway. A single homologue of this gene, TEP1 (YNL128w) ex ists in the budding yeast Saccharomyces cerevisiae. Yeast strains deleted f or TEP1 exhibit essentially no phenotype in haploids; however, diploids exh ibit resistance to the phosphatidylinositol-3-phosphate kinase inhibitor wo rtmannin and to lithium ions. Although rates of cancer increase with age, n either tep1 haploids nor diploids have altered life spans. TEP1 RNA is pres ent throughout the cell cycle, and levels are dramatically up-regulated dur ing meiotic development. Although homozygous tep1 mutants initiate the meio tic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the s urface. introduction of a common PTEN mutation found in human tumors into t he analogous position in Tep1p produces a nonfunctional protein based on in vivo activity. These studies implicate Tep1p in a specific developmental t rafficking or deposition event and suggest that Tep1p, like its mammalian c ounterpart, impinges on the phosphatidylinositol pathway.