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TAOK3 promotes ccRCC progression by phosphorylating ASAP2.

Xiaoli Zheng1, Jing Cheng2, Manman Zhang2

  • 1Department of Pharmacy, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou city University, Hangzhou, 310015, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|March 18, 2026
PubMed
Summary

Thousand and one amino acid protein kinase 3 (TAOK3) drives clear cell renal cell carcinoma (ccRCC) progression by phosphorylating ASAP2. Targeting the TAOK3-ASAP2 pathway may offer new treatments for metastatic ccRCC.

Keywords:
ASAP2MetastasisPhosphorylationTAOK3ccRCC

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype, known for its high metastatic potential and poor prognosis.
  • Understanding the molecular drivers of ccRCC progression is crucial for developing effective therapies.

Purpose of the Study:

  • To identify novel molecular regulators of ccRCC progression.
  • To elucidate the role of thousand and one amino acid protein kinase 3 (TAOK3) in ccRCC.
  • To investigate the TAOK3-ASAP2 signaling axis in ccRCC metastasis.

Main Methods:

  • Gene expression analysis in ccRCC tissues and cell lines.
  • Gain- and loss-of-function assays to assess TAOK3's impact on ccRCC cell behavior.
  • Immunoprecipitation and immunofluorescence to study protein interactions.
  • Mass spectrometry and phosphosite prediction to identify phosphorylation sites.

Main Results:

  • TAOK3 is significantly overexpressed in ccRCC tumors and cell lines.
  • TAOK3 promotes ccRCC cell proliferation, migration, and invasion.
  • TAOK3 interacts with ASAP2 and phosphorylates it at specific serine residues (S701, S712, S722, S728).
  • TAOK3-mediated ASAP2 phosphorylation is essential for ccRCC cell metastasis.

Conclusions:

  • TAOK3 acts as a critical oncogenic regulator in ccRCC.
  • A novel TAOK3-dependent phosphorylation mechanism drives ccRCC progression.
  • The TAOK3-ASAP2 signaling axis represents a potential therapeutic target for metastatic ccRCC.