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Volume 272, Number 47, Issue of November 21, 1997 pp. 29403-29406
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
A Family of Putative Tumor Suppressors Is Structurally and Functionally Conserved in Humans and Yeast

(Received for publication, August 15, 1997, and in revised form, September 15, 1997)

Liwu Li Dagger , Brian R. Ernsting Dagger , Matthew J. Wishart , Daniel L. Lohse Dagger and Jack E. Dixon Dagger

From the Departments of Dagger  Biological Chemistry and  Physiology, University of Michigan, Ann Arbor, Michigan 48109-0606

In Saccharomyces cerevisiae the CDC14 gene is essential for cell cycle progression. Strains carrying the cdc14-1ts allele enter the cell cycle and arrest at restrictive temperatures. We have identified two human cDNAs encoding proteins which share sequence identity to the yeast CDC14p. The cell cycle arrest in cdc14-1ts can be specifically complemented by the human cDNAs suggesting that they are functionally equivalent to the yeast CDC14 gene. Another clone identified in the search for human CDC14-like proteins corresponded to the putative tumor suppressor gene PTEN/MMAC1 (phosphatase and tensin homologue deleted on chromosome 10 or mutated in multiple advanced cancers 1). Analysis of the PTEN/MMAC1 showed that it did not complement the cdc14-1ts allele and that it is more closely related to the yeast open reading frame YNL128W. Human CDC14p and PTEN/MMAC1 were expressed as recombinant proteins, and both were shown to have kinetic properties characteristic of dual specific phosphatases. The human CDC14p was localized in the nucleus while PTEN/MMAC1 has been reported to be localized in the cytoplasm. Our results suggest that CDC14 and YNL128W/PTEN/MMAC1 represent two related, but distinct, families of human and yeast phosphatases.


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