Assessment of PTEN tumor suppressor activity in nonmammalian models: the year of the yeast

Abstract

Model organisms have emerged as suitable and reliable biological tools to study the properties of proteins whose function is altered in human disease. In the case of the PI3K and PTEN human cancer-related proteins, several vertebrate and invertebrate models, including mouse, fly, worm and amoeba, have been exploited to obtain relevant functional information that has been conserved from these organisms to humans along evolution. The yeast Saccharomyces cerevisiae is an eukaryotic unicellular organism that lacks a canonical mammalian-like PI3K/PTEN pathway and PIP3 as a physiological second messenger, PIP2 being essential for its life. The mammalian PI3K/PTEN pathway can be reconstituted in S. cerevisiae, generating growth alteration phenotypes that can be easily monitored to perform in vivo functional analysis of the molecular constituents of this pathway. Here, we review the current nonmammalian model systems to study PTEN function, summarize our knowledge of PTEN orthologs in yeast species and propose the yeast S. cerevisiae as a sensitive biological sensor of PI3K oncogenicity and PTEN tumor suppressor activity.

Tumor suppressors: enhancers or suppressors of regeneration?

“…Heterozygous mice or mice conditionally mutant for Pten develop hyperplasia, and exhibit reduced apoptosis and overgrowth phenotypes in multiple tissues and organs. Similar phenotypes are also observed upon mutation of the Drosophila, nematode, planaria, Xenopus and zebrafish Pten homologs (reviewed by Cid et al, 2008). Pten has not been identified and functions have not yet been studied in urodele amphibians.…”

A Novel Human Dynactin-Associated Protein, dynAP, Promotes Activation of Akt, and Ergosterol-Related Compounds Induce dynAP-Dependent Apoptosis of Human Cancer Cells

“…Many proteins linked with accelerated proliferation of human cancer cells repress the growth of yeast (1)(2)(3). These observations have provided a cell-based high-throughput screening system for anticancer drugs because inhibitors of human proteins can be screened by simply monitoring the restoration of yeast proliferation (4).…”

Examination of the relevance of PI3K and PTEN pathway in Ustilago maydis.

“…pombe (Cid et al, 2008). Also, the possible roles involving PI3K Class III orthologue Vps34 and interaction in other cellular processes have yet to be examined in U. maydis.…”

“…The role of Vps34 in the conversion of PIP2 to PIP3 has been implied in studies using Sch. pombe and a similar role could be observed in U. maydis (Cid et al, 2008). To test this hypothesis the following experiments could be performed:…”

“…(Christoforidis et al, 1999 Vps34 has been shown to be involved in regulation of vesicular trafficking and recruitment of proteins to intracellular membranes involved in the endosomal/lysosomal system (Lindmo and Stenmark, 2006;Odorizzi et al, 2000). Vps34 has also been implicated in nutrient sensing involved with the mTOR pathway in mammalian cells, trimeric G-protein signaling to MAPK in yeast, and autophagy in yeast and higher organisms (Backer, 2008 suggested to possibly involve the class III PI3K (Vps34) (Cid et al, 2008). It is possible that even though there is no Class I PI3K in U. maydis that the class III PI3K may act similar to previous studies using Sch.…”