Chemical and structural approaches to investigate PTEN function and regulation.

Phosphatase and tensin homolog is a lipid phosphatase that serves as the major negative regulator of the PI3K/AKT pathway. It catalyzes the 3'-specific dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to generate PIP2. PTEN's lipid phosphatase function depends on several domains, including an N-terminal segment spanning the first 24 amino acids, which results in a catalytically impaired enzyme when mutated. Furthermore, PTEN is regulated by a cluster of phosphorylation sites located on its C-terminal tail at Ser380, Thr382, Thr383, and Ser385, which drives its conformation from an open to a closed autoinhibited but stable state. Herein, we discuss the protein chemical strategies we used to reveal the structure and mechanism of how PTEN's terminal regions govern its function. Copyright © 2023 Elsevier Inc. All rights reserved.

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Thibault Viennet, Santiago Rodriguez Ospina, Yunqi Lu, Anna Cui, Haribabu Arthanari, Daniel R Dempsey. Chemical and structural approaches to investigate PTEN function and regulation. Methods in enzymology. 2023;682:289-318

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PMID: 36948705

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