Structural mechanisms of PTEN regulation

Glenn R. Masson (Lead / Corresponding author), Roger L. Williams

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) is a tightly regulated enzyme responsible for dephosphorylating the progrowth lipid messenger molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. The carboxy-terminal tail (CTT) of PTEN is key for regulation of the enzyme. When phosphorylated, the unstructured CTT interacts with the phosphatase-C2 superdomain to inactivate the enzyme by preventing membrane association. PTEN mutations associated with cancer also inactivate the enzyme. Alternate translation-initiation sites generate extended isoforms of PTEN, such as PTEN-L that has multiple roles in cells. The extended amino-terminal region bears a signal sequence and a polyarginine sequence to facilitate exit from and entry into cells, respectively, and a membrane-binding helix that activates the enzyme. This amino-terminal region also facilitates mitochondrial and nucleolar localization. This review explores PTEN structure and its impact on localization and regulation.

Original languageEnglish
Article numbera036152
JournalCold Spring Harbor Perspectives in Medicine
Volume10
Issue number3
Early online date21 Oct 2019
DOIs
Publication statusPublished - Mar 2020

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