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Structural Mechanisms of PTEN Regulation.

Glenn R MassonRoger L Williams
Published in: Cold Spring Harbor perspectives in medicine (2020)
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.
Keyphrases
  • pi k akt
  • cell proliferation
  • cell cycle arrest
  • induced apoptosis
  • signaling pathway
  • oxidative stress
  • squamous cell carcinoma
  • transcription factor
  • dna methylation
  • fatty acid
  • cell death
  • genome wide
  • childhood cancer