Cited by 867Cell death mechanisms and regulationProtein Kinase Regulation and GTPase SignalingNF-κB Signaling Pathways

The Role of c-Jun N-terminal Kinase (JNK) in Apoptosis Induced by Ultraviolet C and γ Radiation

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Chen, Yi-Rong, Wang, Xiaoping, Templeton, Dennis, Davis, Roger J., Tan, Tse-Hua·1996·Journal of Biological Chemistry

Abstract

c-Jun N-terminal kinases (JNKs) participate in cellular responses to mitogenic stimuli, environmental stresses, and apoptotic agents. The mechanisms by which JNK integrates with other signaling pathways and regulates the diverse cellular events are unclear. We found JNK, but not p38-mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase 2, to be persistently activated in apoptosis induced by gamma radiation, UV-C, and anti-Fas treatment. Direct correlation was found between JNK activation and apoptosis induced by UV-C and gamma radiation; however, JNK induction and apoptosis induced by Fas signaling were not well correlated. Overexpression of activated JNK1 caused cell death in transfected cells, and the expression of a dominant-negative mutant of MAPK kinase 1 or JNK1 (but not a dominant-negative mutant of p38-MAPK or c-Raf) prevented the UV-C- and gamma radiation-induced cell death. The inductions of JNK in T-cell activation and apoptosis were distinguished by the different activation patterns, transient versus persistent, respectively. Co-treatment with a tyrosine phosphatase inhibitor (sodium orthovanadate) and T-cell activation signals (phorbol 12-myristate 13-acetate plus ionomycin) prolonged JNK induction, followed by T-cell apoptosis. Our data revealed the requirement of the JNK pathway in radiation-induced apoptosis and implicated the importance of the duration of JNK activation in determining the cell fates.

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Crossref · 10.1074/jbc.271.50.31929

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  • Prolonged activation of SAPK can lead to apoptosis.

    “Although the SAPKs can also mediate proliferative responses, prolonged activation of these SAPK can lead to apoptosis (80, 162).”

    From Redox regulation of mitochondrial function (2012) · cites this paper as [80]

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Authors
Chen, Y.-R., Wang, X., Templeton, D., Davis, R. J., & Tan, T.-H.
Affiliations
  • Baylor College of Medicine (US)
  • Case Western Reserve University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Tan, Tse-Hua
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1996-12
Volume
271
Issue
50
Pages
31929-31936
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2074169536
Cited by
867
References
44
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 12 · 2018: 8 · 2017: 7 · 2016: 16 · 2015: 8 · 2014: 14 · 2013: 23 · 2012: 22
FWCI
24.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ai038649-04, 5r01gm049875-04)
  • National Institute of General Medical Sciences (R01-GM-49875)
  • National Institute of Allergy and Infectious Diseases (R01AI38649)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
c-Jun N-terminal kinase, JNK1, apoptosis, ultraviolet C radiation, gamma radiation, Fas-mediated apoptosis, MAPK signaling, p38 MAPK, ERK2, T cell activation, radiation-induced cell death, protein tyrosine phosphatase inhibition, sodium orthovanadate, dominant-negative mutant, cell fate determination
MeSH terms
Cell Division, Enzyme Activation, Gamma Rays, Humans, Phosphoric Monoester Hydrolases, Ultraviolet Rays, Mutagenesis, Apoptosis, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, CD28 Antigens, Jurkat Cells, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 1, DNA Fragmentation

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