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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
Summary
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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