Related Experiment Video

Updated: May 1, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

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The E3 ubiquitin ligase NEDD4 negatively regulates HER3/ErbB3 level and signaling

Z Huang1, B-K Choi1, K Mujoo1

  • 1Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.

Oncogene
|March 26, 2014
PubMed

Insights

Neural precursor cell expressed, developmentally downregulated 4 (NEDD4) ubiquitin ligase targets HER3/ErbB3. Low NEDD4 levels increase HER3 signaling and cancer growth, predicting anti-HER3 antibody therapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • HER3/ErbB3 is a key cancer driver and therapeutic target.
  • Understanding HER3 regulation is crucial for cancer therapy.

Purpose of the Study:

  • Identify novel regulators of HER3.
  • Investigate the role of NEDD4 in HER3 signaling and cancer.

Main Methods:

  • Molecular and biochemical assays to study HER3-NEDD4 interaction.
  • Short hairpin RNA (shRNA) knockdown of NEDD4 in cancer cells.
  • In vitro and in vivo proliferation assays.
  • Analysis of patient tumor tissues.

Main Results:

  • NEDD4 directly interacts with HER3 via its WW domains.
  • NEDD4 knockdown increases HER3 levels, signaling, and cancer cell proliferation.
  • Inverse correlation between HER3 and NEDD4 expression in prostate cancer.
  • NEDD4 knockdown enhances sensitivity to anti-HER3 antibodies.

Conclusions:

  • NEDD4 is a novel ubiquitin E3 ligase for HER3.
  • Low NEDD4 expression correlates with HER3 activation and increased cancer proliferation.
  • NEDD4 levels may predict response to anti-HER3 antibody therapies.

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