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Regulation of the Phosphatidylinositide 3-Kinase Pathway by the Lipid Phosphatase PTEN

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Featured Article: Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998;95:29–39.4

PTEN is a lipid phosphatase whose action targets phosphatidylinositol 3,4,5-trisphosphate (PIP3),5 a component of the lipid cellular membrane. Its role as a tumor suppressor was defined in 1998 in the article by Stambolic et al. highlighted here (1), which reported the extensive effects of the disruption of PTEN (phosphatase and tensin homolog) in mice. By the late 1990s, a quest for the major tumor suppressor gene within the frequently deleted region of chromosome 10 found in advanced cancers culminated in the discovery of PTEN, named based on amino acid sequence homology with the protein tyrosine phosphatases and tensin (1).

The observations reported in the 1998 article contributed to the understanding of the cellular functions of PTEN and the severity of the consequences associated with PTEN loss. Homozygous …

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