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Updated: Aug 19, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

PTEN: a novel anti-oncogenic function independent of phosphatase activity

Koichi Okumura1, Mujun Zhao, Ronald A DePinho

  • 1Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, La Jolla, California 92093-0660, USA.

Cell Cycle (Georgetown, Tex.)
|March 9, 2005
PubMed

Insights

The PTEN gene, a tumor suppressor, interacts with MSP58. This interaction suppresses MSP58-driven transformation, revealing PTEN

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The PTEN gene is a critical tumor suppressor frequently mutated in various cancers.
  • PTEN's known functions involve protein and phosphoinositol phosphatase activity, regulating cell growth.
  • Mutations in PTEN's carboxy-terminus affect its stability, localization, and interaction with other proteins, independent of its catalytic activity.

Purpose of the Study:

  • To identify novel proteins interacting with the PTEN carboxy-terminus.
  • To investigate the functional consequences of PTEN-interacting proteins on tumor suppressor functions.
  • To explore PTEN's mechanisms of action beyond its enzymatic activity.

Main Methods:

  • Protein-protein interaction studies to identify binding partners of the PTEN carboxy-terminus.
  • Functional assays to assess the impact of identified interactions on cellular transformation.
  • Enzymatic activity assays to differentiate between catalytic-dependent and -independent PTEN functions.

Main Results:

  • Identification of MSP58, a v-jun transcriptional target, as a novel interactor of the PTEN carboxy-terminus.
  • Demonstration that PTEN binding to MSP58 suppresses MSP58-mediated cellular transformation.
  • Evidence that PTEN's suppression of MSP58-mediated transformation does not require its phosphatase catalytic activity.

Conclusions:

  • The PTEN carboxy-terminus interacts with MSP58, modulating its oncogenic potential.
  • PTEN possesses functions independent of its enzymatic activity, potentially through protein interactions.
  • These findings suggest novel therapeutic strategies targeting PTEN's non-catalytic functions in cancer.

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