Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic cell transformation

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Updated: Jun 6, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Kangdong Liu1, Yong-Yeon Cho, Ke Yao

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

The Journal of Biological Chemistry
|November 25, 2010
PubMed

Insights

Ribosomal S6 kinase 2 (RSK2) phosphorylates ATF1, promoting cell transformation. The natural compound eriodictyol inhibits this RSK2-ATF1 signaling pathway, offering a potential strategy for cancer prevention.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase involved in cell proliferation.
  • Neoplastic cell transformation is a critical step in cancer development.

Purpose of the Study:

  • To identify novel substrates of RSK2.
  • To investigate the role of RSK2-ATF1 signaling in EGF-induced neoplastic cell transformation.
  • To evaluate eriodictyol as a potential inhibitor of RSK2 signaling.

Main Methods:

  • In vitro kinase assays and pulldown assays.
  • Site-directed mutagenesis and docking experiments.
  • Cellular assays including Western blotting and focus formation assays.

Main Results:

  • ATF1 was identified as a novel substrate of RSK2, phosphorylated at Ser-63, enhancing its transcriptional activity.
  • Eriodictyol specifically inhibited RSK2 kinase activity by binding to its N-terminal kinase domain, suppressing ATF1 phosphorylation.
  • Eriodictyol, RSK2 knockdown, or ATF1 knockdown inhibited EGF- and Ras-mediated neoplastic cell transformation.

Conclusions:

  • RSK2-ATF1 signaling is crucial for neoplastic cell transformation.
  • Eriodictyol effectively suppresses RSK2 kinase activity and downstream signaling.
  • Eriodictyol represents a potential natural therapeutic agent for inhibiting cancer development.

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