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*
Division of Clinical Immunology and Allergy, Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095;
Department of Internal Medicine and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242; and
La Jolla Institute of Allergy and Immunology, San Diego, CA 92121
T lymphocytes undergo apoptosis in response to cellular stress, including UV exposure and gamma irradiation. However, the mechanism by which stress stimuli induce apoptosis is not well understood. While stress stimuli induce the activation of the c-Jun N-terminal kinase (JNK) pathway, it is not clear whether the JNK cascade is activated as a result of cell death or whether the cascade participates in inducing apoptosis. Using a Jurkat T cell line transfected with dominant active (DA)-mitogen-activated protein kinase kinase kinase (MEKK1) in a tetracycline-regulated expression system, we found that expression of DA-MEKK1 results in the apoptosis of Jurkat cells in parallel with prolonged JNK activation. Moreover, DA-MEKK1 induced Fas ligand (FasL) cell surface and mRNA expression, as well as FasL promoter activation. Interference with Fas/FasL interaction prevented DA-MEKK1-mediated apoptosis. In comparing the effect of different stress stimuli to DA-MEKK1, we found that UV, gamma irradiation, and anisomycin prolonged JNK activation in parallel with FasL expression and onset of cell death. In addition, these stimuli also enhance cell surface expression of FasL. Interference with Fas/FasL interactions inhibited anisomycin but not UV- or gamma irradiation-induced apoptosis. Our data show that while the JNK pathway contributes to stress-induced apoptosis in T lymphocytes by regulating FasL expression, not all stress stimuli use the same cell death pathway.
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R. D. Glick, S. L. Swendeman, D. C. Coffey, R. A. Rifkind, P. A. Marks, V. M. Richon, and M. P. La Quaglia Hybrid Polar Histone Deacetylase Inhibitor Induces Apoptosis and CD95/CD95 Ligand Expression in Human Neuroblastoma Cancer Res., September 1, 1999; 59(17): 4392 - 4399. [Abstract] [Full Text] [PDF]
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M. T. Abreu-Martin, A. Chari, A. A. Palladino, N. A. Craft, and C. L. Sawyers Mitogen-Activated Protein Kinase Kinase Kinase 1 Activates Androgen Receptor-Dependent Transcription and Apoptosis in Prostate Cancer Mol. Cell. Biol., July 1, 1999; 19(7): 5143 - 5154. [Abstract] [Full Text] [PDF]
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S. J. Kempiak, T. S. Hiura, and A. E. Nel The Jun Kinase Cascade Is Responsible for Activating the CD28 Response Element of the IL-2 Promoter: Proof of Cross-Talk with the I{kappa}B Kinase Cascade J. Immunol., March 15, 1999; 162(6): 3176 - 3187. [Abstract] [Full Text] [PDF]
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H. Le-Niculescu, E. Bonfoco, Y. Kasuya, F.-X. Claret, D. R. Green, and M. Karin Withdrawal of Survival Factors Results in Activation of the JNK Pathway in Neuronal Cells Leading to Fas Ligand Induction and Cell Death Mol. Cell. Biol., January 1, 1999; 19(1): 751 - 763. [Abstract] [Full Text] [PDF]
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 C. WIDMANN, S. GIBSON, M. B. JARPE, and G. L. JOHNSON Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human Physiol Rev, January 1, 1999; 79(1): 143 - 180. [Abstract] [Full Text] [PDF]
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T. Kasai, K. Ohguchi, S. Nakashima, Y. Ito, T. Naganawa, N. Kondo, and Y. Nozawa Increased Activity of Oleate-Dependent Type Phospholipase D During Actinomycin D-Induced Apoptosis in Jurkat T Cells J. Immunol., December 15, 1998; 161(12): 6469 - 6474. [Abstract] [Full Text] [PDF]
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M. Faris, K. M. Latinis, S. J. Kempiak, G. A. Koretzky, and A. Nel Stress-Induced Fas Ligand Expression in T Cells Is Mediated through a MEK Kinase 1-Regulated Response Element in the Fas Ligand Promoter Mol. Cell. Biol., September 1, 1998; 18(9): 5414 - 5424. [Abstract] [Full Text]
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T. Hatai, A. Matsuzawa, S. Inoshita, Y. Mochida, T. Kuroda, K. Sakamaki, K. Kuida, S. Yonehara, H. Ichijo, and K. Takeda Execution of Apoptosis Signal-regulating Kinase 1 (ASK1)-induced Apoptosis by the Mitochondria-dependent Caspase Activation J. Biol. Chem., August 18, 2000; 275(34): 26576 - 26581. [Abstract] [Full Text] [PDF]
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Y. Chen and M.-Z. Lai c-Jun NH2-terminal Kinase Activation Leads to a FADD-dependent but Fas Ligand-independent Cell Death in Jurkat T Cells J. Biol. Chem., March 9, 2001; 276(11): 8350 - 8357. [Abstract] [Full Text] [PDF]
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M. M. Kavurma, F. S. Santiago, E. Bonfoco, and L. M. Khachigian Sp1 Phosphorylation Regulates Apoptosis via Extracellular FasL-Fas Engagement J. Biol. Chem., February 9, 2001; 276(7): 4964 - 4971. [Abstract] [Full Text] [PDF]
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