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Updated: May 2, 2026

Detection of Protein Ubiquitination
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Detection of Protein Ubiquitination

Published on: August 19, 2009

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NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN

Xinjiang Wang1, Lloyd C Trotman, Theresa Koppie

  • 1Cell Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 522, New York, NY 10021, USA.

Cell
|January 16, 2007
PubMed

Insights

The tumor suppressor PTEN

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The tumor suppressor PTEN is crucial for cellular processes and frequently altered in cancers.
  • Reduced PTEN expression significantly impacts carcinogenesis.
  • PTEN's role in cancer necessitates understanding its regulatory mechanisms.

Purpose of the Study:

  • To elucidate the regulatory mechanism of PTEN protein levels.
  • To identify the ubiquitin ligase responsible for PTEN degradation.
  • To investigate the role of NEDD4-1 in PTEN regulation and cancer.

Main Methods:

  • Ubiquitin-mediated proteasomal degradation assays.
  • Purification and identification of PTEN's ubiquitin ligase.
  • Cellular transformation assays.
  • Analysis of NEDD4-1 expression in cancer models and human samples.
  • Xenotransplanted tumor growth inhibition assays.

Main Results:

  • PTEN levels are regulated by ubiquitin-mediated proteasomal degradation.
  • NEDD4-1 was identified as the ubiquitin ligase for PTEN.
  • NEDD4-1 catalyzes PTEN polyubiquitination, reducing PTEN stability.
  • Overexpression of NEDD4-1 promoted cellular transformation.
  • High NEDD4-1 expression correlated with low PTEN levels in PTEN-normal cancers.
  • NEDD4-1 elimination inhibited tumor growth dependently on PTEN.

Conclusions:

  • NEDD4-1 negatively regulates PTEN stability through ubiquitination.
  • Aberrant NEDD4-1 upregulation can suppress PTEN in cancer.
  • NEDD4-1 acts as a proto-oncogene by targeting PTEN.
  • NEDD4-1 represents a potential therapeutic target in cancers with low PTEN.

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