A FAMILY OF PUTATIVE TUMOR SUPPRESSORS IS STRUCTURALLY AND FUNCTIONALLY CONSERVED IN HUMANS AND YEAST

In Saccharomyces cerevisiae the CDC14 gene is essential for cell cycle progression, Strains carrying the cdc14-1(ts) allele enter the cell c ycle and arrest at restrictive temperatures, We have identified two hu man cDNAs encoding proteins which share sequence identity to the yeast CDC14p. The cell cycle arrest in cdc14-1(ts) can be specifically comp lemented by the human cDNAs suggesting that they are functionally equi valent to the yeast CDC14 gene, Another clone identified in the search for human CDC14-like proteins corresponded to the putative tumor supp ressor gene PTEN/MMAC1 (phosphatase and tensin homologue deleted on ch romo same 10 or mutated in multiple advanced cancers 1), Analysis of t he PTEN/MMAC1 showed that it did not complement the cdc14-1(ts) allele and that it is more closely related to the yeast open reading frame Y NL128W. Human CDC14p and PTEN/MMAC1 were expressed as recombinant prot eins, and both were shown to have kinetic properties characteristic of dual specific phosphatases, The human CDC14p was localized in the nuc leus while PTEN/MMAC1 has been reported to be localized in the cytopla sm, Our results suggest that CDC14 and YNL128W/PTEN/MMAC1 represent tw o related, but distinct, families of human and yeast phosphatases.