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c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms
R Wisdom1, R S Johnson, C Moore
1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
The EMBO Journal
|January 7, 1999
Summary
The transcription factor c-Jun is essential for cell growth by regulating cyclin D1 and prevents cell death from UV radiation or TNFalpha. Its role in cell cycle progression is independent of specific phosphorylation sites, but apoptosis protection requires them.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- c-Jun is a key component of the transcription factor AP-1.
- AP-1 activation is triggered by diverse extracellular stimuli.
- c-Jun regulation involves protein level changes and phosphorylation by Jun N-terminal kinase (JNK).
Purpose of the Study:
- To investigate the role of c-Jun in fibroblast cell growth and apoptosis.
- To elucidate the molecular mechanisms underlying c-Jun's functions in these processes.
Main Methods:
- Utilized fibroblasts derived from c-Jun null embryos.
- Assessed cell cycle progression (G1 phase).
- Analyzed transcriptional control of the cyclin D1 gene.
- Investigated apoptosis in response to UV radiation and tumor necrosis factor alpha (TNFalpha).
Main Results:
- c-Jun is required for G1 phase progression in fibroblasts via transcriptional control of the cyclin D1 gene.
- c-Jun protects cells from UV-induced apoptosis.
- c-Jun cooperates with NF-kappaB to prevent TNFalpha-induced apoptosis.
- G1 progression is independent of c-Jun serine 63/73 phosphorylation.
- Apoptosis protection from UV requires c-Jun serine 63/73 phosphorylation.
Conclusions:
- c-Jun plays critical, distinct roles in cell growth and apoptosis.
- Different extracellular stimuli utilize distinct biochemical mechanisms to target c-Jun.
- c-Jun links growth factor signaling to cell cycle regulators and impacts cell survival pathways.