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Updated: Jul 11, 2026

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation

Ke Yao1, Yong-Yeon Cho, H Robert Bergen

  • 1Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.

Cancer Research
|September 19, 2007
PubMed

Insights

Nuclear factor of activated T3 (NFAT3) is phosphorylated by c-jun-NH(2)-kinases (JNK1/2), regulating its activity. NFAT3 demonstrates anti-oncogenic potential by suppressing tumor cell transformation and foci formation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • c-jun-NH(2)-kinases (JNK) are crucial in cell transformation and apoptosis.
  • The role of nuclear factor of activated T3 (NFAT3) in JNK-mediated oncogenesis is not fully understood.

Purpose of the Study:

  • To investigate the interaction between JNK and NFAT3.
  • To elucidate the functional consequences of JNK-mediated NFAT3 phosphorylation.
  • To determine the role of NFAT3 in JNK-induced cell transformation.

Main Methods:

  • Phosphorylation site mapping of NFAT3 by JNK1/2.
  • Reporter gene assays to assess NFAT3 transcriptional activity.
  • Gene knockdown and ectopic expression studies in NIH3T3 and MEF cells.
  • JNK inhibitor treatment.

Main Results:

  • JNK1/2 phosphorylate NFAT3 at Ser(213) and Ser(217) within its transactivation domain.
  • JNK1/2 enhance NFAT3 transcriptional activity; mutations at phosphorylation sites abolish this.
  • NFAT3 suppresses JNK-induced foci formation and AP-1 activity.
  • Knockdown of JNK1/2 or NFAT3 modulates cell transformation.

Conclusions:

  • JNK directly phosphorylates and activates NFAT3.
  • NFAT3 acts as a tumor suppressor by inhibiting JNK-driven oncogenic processes.
  • NFAT3 exhibits anti-oncogenic potential, offering therapeutic targets.

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