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Updated: Jul 13, 2025

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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ATXN3 deubiquitinates YAP1 to promote tumor growth

Shengnan Wang1,2, Kun Liu2, Xiaohua Han3

  • 1College of Basic Medical Sciences, Dalian Medical University Dalian 116044, Liaoning, China.

American Journal of Cancer Research
|October 11, 2023
PubMed

Insights

Ataxin-3 (ATXN3) deubiquitinase activity stabilizes Yes-associated protein 1 (YAP1), promoting cancer cell growth and migration. Targeting ATXN3 may offer a new strategy for antitumor chemotherapy.

Area of Science:

  • Molecular Oncology
  • Biochemistry
  • Cancer Biology

Background:

  • Ataxin-3 (ATXN3), a deubiquitinating enzyme, is implicated as an oncogene in various human cancers.
  • The precise molecular mechanisms by which ATXN3 promotes tumorigenesis are not fully understood.

Purpose of the Study:

  • To elucidate the role of ATXN3 in cancer progression.
  • To identify the molecular targets and pathways regulated by ATXN3 in cancer cells.

Main Methods:

  • CRISPR-Cas9 gene editing was employed to delete the ATXN3 gene in cancer cells.
  • Quantitative analysis of protein and mRNA expression, including YAP1 and its target genes (CTGF, CYR61).
  • Co-immunoprecipitation assays to investigate the interaction between ATXN3 and YAP1.
  • Immunohistochemistry to assess ATXN3 and YAP1 expression in human cancer tissues.

Main Results:

  • ATXN3 deletion led to decreased YAP1 protein levels without affecting YAP1 mRNA transcription.
  • ATXN3 suppression selectively reduced the expression of YAP1 target genes, CTGF and CYR61.
  • ATXN3 interacts with YAP1, protecting it from ubiquitination and subsequent degradation.
  • Cancer cell growth and migration were inhibited by ATXN3 suppression and could be rescued by YAP1 reconstitution.
  • A positive correlation between ATXN3 and YAP1 protein expression was observed in human breast and pancreatic cancers.

Conclusions:

  • ATXN3 functions as a deubiquitinase for YAP1, stabilizing it and promoting cancer cell proliferation, migration, and angiogenesis.
  • ATXN3 is a novel regulator of YAP1 stability in tumorigenesis.
  • ATXN3 represents a potential therapeutic target for developing new antitumor strategies.
Keywords:
ATXN3YAP1cancerdeubiqutinase

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