Florence Solari et al. (2002) European Worm Meeting "The human PTEN tumor suppressor regulates diapause and longevity in Caenorhabditis elegans."

Florence Solari, Marc Billaud, Angelique Bourbon-Piffaut

[European Worm Meeting, 2002]

The tumor suppressor gene PTEN (also called MMAC1 or TEP1) is somatically mutated in a variety of cancers. In addition, germline mutations of PTEN are responsible for two dominantly inherited cancer syndromes called Cowden disease and Bannayan-Zonana syndrome. PTEN encodes a protein which displays both a dual-specificity protein phosphatase and a lipid phosphatase activities. PTEN antagonizes phosphatidylinositol-3 kinase (PI3K) by catalyzing the hydrolysis of the phosphate on position D3 of phosphatidylinositol (3, 4, 5) triphosphate (PIP3). We and others have recently shown that DAF-18, the orthologue of PTEN in C. elegans, is a component of the insulin-like signalling pathway that controls the entry into dauer and adult longevity. Daf-18 mutants are dauer defective and have a shorter lifespan than wild type worms. Although PTEN and DAF-18 proteins share the highest homology within the catalytic domain, they do not exhibit a marked similarity outside this region. Notably, the C-terminus of PTEN, which mediates interaction with PDZ domain proteins and regulates the protein stability, is not conserved in DAF-18. We now report that PTEN can substitute to DAF-18 in C.elegans and we are using the nematode to uncover the mode of regulation of PTEN.