The Role of c-Jun N-terminal Kinase (JNK) in Apoptosis Induced by Ultraviolet C and γ Radiation
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Cites
Apoptosis in the Pathogenesis and Treatment of Disease
Thompson, C. B. (1995) · Science · doi:10.1126/science.7878464 · Cited by 6,524 · see citing works
Vermes, I., Haanen, C., Steffens-Nakken, H. M., & Reutellingsperger, C. (1995) · Journal of Immunological Methods · doi:10.1016/0022-1759(95)00072-i · Cited by 5,437 · see citing works
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995) · Science · doi:10.1126/science.270.5240.1326 · Cited by 5,290 · see citing works
Self-citationMarshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 4,557 · see citing works
Nagata, S., & Golstein, P. (1995) · Science · doi:10.1126/science.7533326 · Cited by 3,979 · see citing works
Dérijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M., & Davis, R. J. (1994) · Cell · doi:10.1016/0092-8674(94)90380-8 · Cited by 3,188 · see citing works
Self-citationp53 is required for radiation-induced apoptosis in mouse thymocytes
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T. (1993) · Nature · doi:10.1038/362847a0 · Cited by 2,864 · see citing works
The stress-activated protein kinase subfamily of c-Jun kinases
Kyriakis, J. M., Banerjee, P. T., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., & Woodgett, J. R. (1994) · Nature · doi:10.1038/369156a0 · Cited by 2,601 · see citing works
Mechanisms and Genes of Cellular Suicide
Steller, H. (1995) · Science · doi:10.1126/science.7878463 · Cited by 2,465 · see citing works
The Regulation of AP-1 Activity by Mitogen-activated Protein Kinases
Karin, M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.28.16483 · Cited by 2,432 · see citing works
Raingeaud, J., Gupta, S., Rogers, J. S., Dickens, M., Han, J., Ulevitch, R. J., & Davis, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7420 · Cited by 2,244 · see citing works
Self-citationThe TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death
Smith, C. A., Farrah, T., & Goodwin, R. G. (1994) · Cell · doi:10.1016/0092-8674(94)90372-7 · Cited by 1,909 · see citing works
Hibi, M., Lin, A., Smeal, T., Minden, A., & Karin, M. (1993) · Genes & Development · doi:10.1101/gad.7.11.2135 · Cited by 1,886 · see citing works
Transcription Factor ATF2 Regulation by the JNK Signal Transduction Pathway
Gupta, S., Campbell, D., Dérijard, B., & Davis, R. J. (1995) · Science · doi:10.1126/science.7824938 · Cited by 1,440 · see citing works
Self-citationRaf-1 activates MAP kinase-kinase
Kyriakis, J. M., App, H., Zhang, X., Banerjee, P. T., Brautigan, D. L., Rapp, U. R., & Avruch, J. (1992) · Nature · doi:10.1038/358417a0 · Cited by 1,263 · see citing works
Sun, H., Charles, C. H., Lau, L. F., & Tonks, N. K. (1993) · Cell · doi:10.1016/0092-8674(93)90383-2 · Cited by 1,156 · see citing works
Integration of MAP Kinase Signal Transduction Pathways at the Serum Response Element
Whitmarsh, A. J., Shore, P., Sharrocks, A. D., & Davis, R. J. (1995) · Science · doi:10.1126/science.7618106 · Cited by 932 · see citing works
Self-citationJNK is involved in signal integration during costimulation of T lymphocytes
Su, B., Jacinto, E., Hibi, M., Kallunki, T., Karin, M., & Ben‐Neriah, Y. (1994) · Cell · doi:10.1016/0092-8674(94)90056-6 · Cited by 907 · see citing works
Traverse, S., Gómez, N., Paterson, H., Marshall, C. J., & Cohen, P. (1992) · Biochemical Journal · doi:10.1042/bj2880351 · Cited by 874 · see citing works
Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase
Keyse, S. M., & Emslie, E. (1992) · Nature · doi:10.1038/359644a0 · Cited by 640 · see citing works
van Dam, H., Wilhelm, D., Herr, I., Steffen, A., Herrlich, P. A., & Angel, P. E. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07168.x · Cited by 598 · see citing works
Activation of the c-Abl tyrosine kinase in the stress response to DMA-damaging agents
Kharbanda, S. M., Ren, R., Pandey, P., Shafman, T. D., Feller, S. M., Weichselbaum, R. R., & Kufe, D. W. (1995) · Nature · doi:10.1038/376785a0 · Cited by 484 · see citing works
Minden, A., Lin, A., Smeal, T., Dérijard, B., Cobb, M. H., Davis, R. J., & Karin, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.6683 · Cited by 467 · see citing works
Self-citationPersistent Activation of c-Jun N-terminal Kinase 1 (JNK1) in γ Radiation-induced Apoptosis
Chen, Y., Meyer, C. F., & Tan, T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.631 · Cited by 460 · see citing works
Self-citationSignal Transduction by Tumor Necrosis Factor Mediated by JNK Protein Kinases
Sluss, H. K., Barrett, T., Dérijard, B., & Davis, R. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8376 · Cited by 457 · see citing works
Self-citationChu, Y., Solski, P. A., Khosravi‐Far, R., Der, C. J., & Kelly, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.11.6497 · Cited by 442 · see citing works
ICE Family Proteases: Mediators of All Apoptotic Cell Death?
Henkart, P. A. (1996) · Immunity · doi:10.1016/s1074-7613(00)80428-8 · Cited by 432 · see citing works
Ceramide Activates the Stress-activated Protein Kinases
Westwick, J. K., Bielawska, A. E., Dbaibo, G. S., Hannun, Y. A., & Brenner, D. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.39.22689 · Cited by 369 · see citing works
Johnson, N. L., Gardner, A. M., Diener, K., Lange, C. A., Gleavy, J., Jarpe, M. B., Minden, A., Karin, M., Zon, L. I., & Johnson, G. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.6.3229 · Cited by 340 · see citing works
Ras-dependent growth factor regulation of MEK kinase in PC12 cells
Lange, C. A., & Johnson, G. L. (1994) · Science · doi:10.1126/science.8073291 · Cited by 321 · see citing works
Liu, Y., Gorospe, M., Yang, C., & Holbrook, N. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.15.8377 · Cited by 283 · see citing works
Milne, D., Campbell, L. E., Campbell, D. G., & Meek, D. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5511 · Cited by 257 · see citing works
Hu, M. C. ‐., Qiu, W., Wang, X., Meyer, C. F., & Tan, T. (1996) · Genes & Development · doi:10.1101/gad.10.18.2251 · Cited by 255 · see citing works
Self-citationNguyen, T. T. H., Scimeca, J., Filloux, C., Peraldi, P., Carpentier, J. L., & OBBERGHEN, E. V. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98418-8 · Cited by 222 · see citing works
Berberich, I., Shu, G. L., Siebelt, F., Woodgett, J. R., Kyriakis, J. M., & Clark, E. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00337.x · Cited by 170 · see citing works
Selective Activation of c-Jun Kinase Mitogen-activated Protein Kinase by CD40 on Human B Cells
Sakata, N., Patel, H. R., Terada, N., Aruffo, A. A., Johnson, G. L., & Gelfand, E. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.51.30823 · Cited by 169 · see citing works
Meyer, C. F., Wang, X., Chang, C., Templeton, D. J., & Tan, T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8971 · Cited by 166 · see citing works
Self-citationBcl-2 and Bcl-x: regulatory switches for lymphoid death and survival
Núñez, G., Merino, R., Grillot, D., & González‐García, M. (1994) · Immunology Today · doi:10.1016/0167-5699(94)90221-6 · Cited by 152 · see citing works
The beta-PDGF receptor induces neuronal differentiation of PC12 cells.
Heasley, L. E., & Johnson, G. L. (1992) · Molecular Biology of the Cell · doi:10.1091/mbc.3.5.545 · Cited by 145 · see citing works
Phenethyl isothiocyanate, a natural chemopreventive agent, activates c-Jun N-terminal kinase 1.
Yu, R., Jiao, J.-J., Duh, J., Tan, T., & Kong, A.-N. T. (1996) · PubMed · Cited by 110 · see citing works
Self-citationAdriamycin activates c-jun N-terminal kinase in human leukemia cells: a relevance to apoptosis
Yu, R., Shtil, A. A., Tan, T., Roninson, I. B., & Kong, A. T. (1996) · Cancer Letters · doi:10.1016/0304-3835(96)04345-5 · Cited by 101 · see citing works
Self-citationConstitutively activated JNK is associated with HTLV-1 mediated tumorigenesis.
Xu, X., Heidenreich, O. T., Kitajima, I., et al. (1996) · PubMed · Cited by 90 · see citing works
Growth factors and cell proliferation
Rozengurt, E. (1992) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(92)90027-a · Cited by 75 · see citing works
A simple assay for examining the effect of transiently expressed genes on programmed cell death
Memon, S. A., Petrak, D., Moreno, M. B., et al. (1995) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)00294-7 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular processing of platinum anticancer drugs
Wang, D., & Lippard, S. J. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1691 · Cited by 3,801 · see citing works
Inhibition of JNK activation through NF-κB target genes
Tang, G., Minemoto, Y., Dibling, B., Purcell, N. H., Li, Z., Karin, M., & Lin, A. (2001) · Nature · doi:10.1038/35104568 · Cited by 721 · see citing works
Kasibhatla, S., Brunner, T., Genestier, L., Echeverri, F., Mahboubi, A., & Green, D. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80054-4 · Cited by 721 · see citing works
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Alcohol and mitochondria: a dysfunctional relationship
Hoek, J. B., Cahill, A., & Pastorino, J. G. (2002) · Gastroenterology · doi:10.1053/gast.2002.33613 · Cited by 553 · see citing works
Sakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., Piao, J., Yagita, H., Okumura, K., Doi, T., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg379 · Cited by 497 · see citing works
Translocation of SAPK/JNK to Mitochondria and Interaction with Bcl-xL in Response to DNA Damage
Kharbanda, S., Saxena, S., Yoshida, K., Pandey, P., Kaneki, M., Wang, Q., Cheng, K., Chen, Y.-N., Campbell, A., Sudha, T., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.322 · Cited by 429 · see citing works
Self-citationGlucose or diabetes activates p38 mitogen-activated protein kinase via different pathways
Igarashi, M., Wakasaki, H., Takahara, N., Ishii, H., Jiang, Z.-Y., Yamauchi, T., Kuboki, K., Meier, M., Rhodes, C. J., & King, G. L. (1999) · Journal of Clinical Investigation · doi:10.1172/jci3326 · Cited by 386 · see citing works
The ASK1-MAP Kinase Cascades in Mammalian Stress Response
Matsukawa, J. (2004) · Journal of Biochemistry · doi:10.1093/jb/mvh134 · Cited by 343 · see citing works
How does radiation kill cells?
Cohen–Jonathan, E., Bernhard, E. J., & McKenna, W. G. (1999) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(99)80014-3 · Cited by 328 · see citing works
Proteasome Inhibitors Activate Stress Kinases and Induce Hsp72
Meriin, A. B., Gabai, V. L., Yaglom, J., Shifrin, V. I., & Sherman, M. Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.11.6373 · Cited by 300 · see citing works
The UV response of the skin: a review of the MAPK, NFκB and TNFα signal transduction pathways
Muthusamy, V., & Piva, T. J. (2010) · Archives of Dermatological Research · doi:10.1007/s00403-009-0994-y · Cited by 265 · see citing works
Guo, Y.-L., Baysal, K., Kang, B., Yang, L.-J., & Williamson, J. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.7.4027 · Cited by 249 · see citing works
Nagata, Y., & Todokoro, K. (1999) · Blood · doi:10.1182/blood.v94.3.853.415a12_853_863 · Cited by 218 · see citing works
Lee, Y. J., & Shukla, S. D. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.12.006 · Cited by 70 · see citing works
Inhibition of the TNF-α^|^ndash;Induced Serine Phosphorylation of IRS-1 at 636/639 by AICAR
Shibata, T., Takaguri, A., Ichihara, K., & Satoh, K. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.12270fp · Cited by 28 · see citing works
- 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
- hybrid
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review