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JNK activation is regulated by E2F and promotes E2F1-induced apoptosis

Dana Bashari1, Dalia Hacohen, Doron Ginsberg

  • 1The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, Israel.

Cellular Signalling
|August 31, 2010
PubMed

Insights

The E2F transcription factor regulates the JNK pathway by increasing GCK kinase expression, which promotes JNK phosphorylation and stress-induced apoptosis. This study reveals a new link between E2F and JNK signaling in cancer.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Biology

Background:

  • E2F transcription factors are crucial targets of the RB tumor suppressor, frequently dysregulated in human cancers.
  • E2F controls cell proliferation and apoptosis and influences signal transduction pathways.

Purpose of the Study:

  • To investigate the role of E2F in modulating the JNK (c-Jun N-terminal kinase) signaling pathway.
  • To identify the molecular mechanisms linking E2F to JNK pathway activity and apoptosis.

Main Methods:

  • Analysis of E2F1 and E2F3 expression and their effect on JNK phosphorylation.
  • Investigated the role of GCK (MAP4K) in mediating E2F-induced JNK activation.
  • Assessed the impact of JNK pathway inhibition on E2F1-induced apoptosis.

Main Results:

  • E2F1 and E2F3 upregulate JNK phosphorylation, while their downregulation inhibits UV-induced JNK phosphorylation.
  • E2F induces JNK phosphorylation through the transcriptional upregulation of the kinase GCK.
  • Inhibition of GCK or JNK significantly impairs E2F1-induced apoptosis.

Conclusions:

  • GCK is identified as a novel E2F-regulated gene.
  • A functional link between the E2F transcription factor and the JNK signaling pathway is established.
  • This interaction plays a critical role in mediating stress-induced apoptosis.

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