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USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer

Ashley Mussell1, He Shen1, Yanmin Chen1

  • 1Department of Cancer Genetics & Genomics, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY 14203, USA.

Cancers
|October 29, 2020
PubMed

Insights

Ubiquitin specific peptidase 1 (USP1) regulates TAZ protein stability, impacting breast cancer cell proliferation and migration. USP1 and TAZ show a positive correlation in patients, suggesting therapeutic potential.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • The Hippo signaling pathway, conserved from Drosophila to mammals, regulates cell growth and organ size.
  • Key effectors YAP/TAZ are frequently dysregulated in cancers, promoting proliferation, migration, and metastasis.
  • Understanding YAP/TAZ protein regulation is crucial for targeting cancer phenotypes.

Purpose of the Study:

  • To identify novel regulators of TAZ (WWTR1) protein at the post-translational level.
  • To investigate the role of deubiquitinating enzymes (DUBs) in TAZ regulation.
  • To explore the therapeutic potential of targeting TAZ regulation in breast cancer.

Main Methods:

  • Conducted an siRNA library screen targeting deubiquitinating enzymes (DUBs).
  • Utilized co-immunoprecipitation to assess protein-protein interactions.
  • Quantified protein levels, ubiquitination status, and cell proliferation/migration assays.
  • Analyzed patient data for correlation between USP1 and TAZ expression.

Main Results:

  • Identified ubiquitin specific peptidase 1 (USP1) as a novel regulator of TAZ.
  • Demonstrated that USP1 interacts with TAZ and enhances its protein stability.
  • USP1 depletion leads to increased TAZ poly-ubiquitination, reduced TAZ levels, and decreased breast cancer cell proliferation and migration.
  • Observed a significant positive correlation between USP1 and TAZ expression in breast cancer patient samples.

Conclusions:

  • USP1 deubiquitinase activity stabilizes TAZ protein, promoting malignant phenotypes in breast cancer.
  • USP1-TAZ interaction represents a potential therapeutic target for breast cancer.
  • Findings elucidate the crosstalk between USP1 and the Hippo pathway, offering insights for novel treatment strategies.
Keywords:
TAZUSP1triple negative breast cancer

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