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Posttranslational Regulation and Conformational Plasticity of PTEN

Larissa Kotelevets1,2, Barbara Trifault3,4,5, Eric Chastre1,2

  • 1Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Saint-Antoine, INSERM UMR S 938 Paris, Hôpital Saint-Antoine, Bâtiment Kourilsky, 75012 Paris, France.

Cold Spring Harbor Perspectives in Medicine
|January 15, 2020
PubMed

Insights

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a crucial tumor suppressor. Understanding PTEN regulation and function is key to developing cancer therapies that restore its tumor-suppressing activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) acts as a tumor suppressor, frequently downregulated in human cancers.
  • PTEN negatively regulates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway via its lipid phosphatase activity.
  • PTEN also exhibits PI3K/AKT-independent functions, including protein-phosphatase activities and nuclear roles, influencing cell proliferation, survival, migration, and invasion.

Purpose of the Study:

  • To review current knowledge on the regulation of PTEN protein levels and function.
  • To explore how PTEN dysregulation contributes to tumorigenesis.
  • To discuss therapeutic strategies for restoring PTEN tumor-suppressor activity in cancer.

Main Methods:

  • Literature review and synthesis of existing research on PTEN.
  • Analysis of posttranslational modifications and conformational changes affecting PTEN.
  • Exploration of therapeutic interventions targeting PTEN.

Main Results:

  • PTEN's tumor-suppressive role is compromised by its down-modulation in cancer.
  • Mechanisms regulating PTEN levels and function are complex, involving posttranslational modifications and conformational plasticity.
  • Restoring PTEN activity presents a promising therapeutic avenue for cancer treatment.

Conclusions:

  • Understanding PTEN's intricate regulatory mechanisms is vital for cancer research.
  • Targeting PTEN offers potential for novel cancer therapies.
  • Further research into PTEN's multifaceted roles can illuminate pathways to combat cancer.

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