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Polyunsaturated fatty acids inhibit PI3K activity in a yeast‐based model system
Author(s) -
Couplan Elodie,
Le Cann Marie,
Le Foll Christelle,
Corporeau Charlotte,
Blondel Marc,
Delarue Jacques
Publication year - 2009
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.200800229
Subject(s) - pi3k/akt/mtor pathway , polyunsaturated fatty acid , yeast , p110α , phosphatidylinositol , pten , biology , biochemistry , context (archaeology) , protein kinase b , protein subunit , chemistry , microbiology and biotechnology , signal transduction , gene , fatty acid , paleontology
The phosphatidylinositol 3‐kinase (PI3K) pathway controls the regulation of cell growth, proliferation, migration and apoptosis. In many tumors, the PI3K gene is mutated or overexpressed, and/or the PI3K pathway is hyperactive. PI3K is therefore a potential pharmacological target for the development of anti‐tumor drugs. Some polyunsaturated fatty acids (PUFA), when given in the diet, may lead to a decrease in PI3K activity. We used a yeast‐based model to reconstitute the PI3K/PTEN/Akt pathway to study the effects of long‐chain polyunsaturated n‐3 fatty acids on PI3K, and found that various PUFA were able to alleviate toxicity induced by overexpression of PI3K. The various PUFA had no significant effect on the steady‐state level of PI3K catalytic subunit proteins (p110α) in yeast. However, depletion of phosphatidylinositol 4,5‐bisphosphate due to overexpression of the p110α subunit was significantly reduced by treating the yeast cells with the various PUFA. The inhibition of mammalian PI3K, expressed in an exogenous cellular context in yeast, is likely to be a direct effect of these PUFA on PI3K rather than on other mammalian endogenous or environmental factors. These results are particularly promising given the abundance of active PUFA in marine foodstuffs and especially fish oils.