This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, T. K. Articles by Yim, J. Search for Related Content PubMed PubMed Citation Articles by Kim, T. K. Articles by Yim, J.

Chemotherapeutic DNA-damaging Drugs Activate Interferon Regulatory Factor-7 by the Mitogen-activated Protein Kinase Kinase-4-c-Jun NH₂-Terminal Kinase Pathway¹

National Creative Research Initiative Center for Genetic Reprogramming, Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea [T. K. K., T. K., T. Y. K., J. K.], and Institute of Chemistry and Cell Biology, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115 [T. K. K., W. G. L.]

Chemotherapeutic drugs and energy-rich radiation cause DNA damage, inducing signaling pathways for apoptotic cell death or cell growth arrest. The tumor suppressor gene p53 plays the critical role in the regulation of these DNA damage responses. Human tumor cells can become resistant to chemotherapy through functional inactivation of p53. Thus, it is important to identify p53-independent DNA damage signaling pathways. Here, treatment of cells with chemotherapeutic drugs or UV irradiation potentiated the transcriptional activity of IFN regulatory factor-7 (IRF7), inducing its phosphorylation and its nuclear translocation. Furthermore, IRF7 was activated by the c-Jun NH₂-terminal kinase (JNK) in response to DNA-damaging agents. Activation of JNK by mitogen-activated protein kinase kinase-4 stimulated the transcriptional activity of IRF7 and induced its translocation into the nucleus. Thus, activation of IRF7 through the JNK signaling pathway may play a role in the transcriptional regulation of genes in response to DNA-damaging agents.

This article has been cited by other articles:

				L. E. Huye, S. Ning, M. Kelliher, and J. S. Pagano Interferon Regulatory Factor 7 Is Activated by a Viral Oncoprotein through RIP-Dependent Ubiquitination Mol. Cell. Biol., April 15, 2007; 27(8): 2910 - 2918. [Abstract] [Full Text] [PDF]

				N. E. Buckley, A. M. Hosey, J. J. Gorski, J. W. Purcell, J. M. Mulligan, D. P. Harkin, and P. B. Mullan BRCA1 Regulates IFN-{gamma} Signaling through a Mechanism Involving the Type I IFNs Mol. Cancer Res., March 1, 2007; 5(3): 261 - 270. [Abstract] [Full Text] [PDF]

				W. Lim, K. Gee, S. Mishra, and A. Kumar Regulation of B7.1 Costimulatory Molecule Is Mediated by the IFN Regulatory Factor-7 through the Activation of JNK in Lipopolysaccharide-Stimulated Human Monocytic Cells J. Immunol., November 1, 2005; 175(9): 5690 - 5700. [Abstract] [Full Text] [PDF]

				S. Uematsu, S. Sato, M. Yamamoto, T. Hirotani, H. Kato, F. Takeshita, M. Matsuda, C. Coban, K. J. Ishii, T. Kawai, et al. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction J. Exp. Med., March 21, 2005; 201(6): 915 - 923. [Abstract] [Full Text] [PDF]

				S. Ning, A. M. Hahn, L. E. Huye, and J. S. Pagano Interferon Regulatory Factor 7 Regulates Expression of Epstein-Barr Virus Latent Membrane Protein 1: a Regulatory Circuit J. Virol., September 1, 2003; 77(17): 9359 - 9368. [Abstract] [Full Text] [PDF]

				T. Y. Kim, K.-H. Lee, S. Chang, C. Chung, H.-W. Lee, J. Yim, and T. K. Kim Oncogenic Potential of a Dominant Negative Mutant of Interferon Regulatory Factor 3 J. Biol. Chem., April 18, 2003; 278(17): 15272 - 15278. [Abstract] [Full Text] [PDF]

				S.-Y. Han, S.-H. Kim, and L. E. Heasley Differential Gene Regulation by Specific Gain-of-function JNK1 Proteins Expressed in Swiss 3T3 Fibroblasts J. Biol. Chem., November 27, 2002; 277(49): 47167 - 47174. [Abstract] [Full Text] [PDF]

				H. N. Andrews, P. B. Mullan, S. McWilliams, S. Sebelova, J. E. Quinn, P. M. Gilmore, N. McCabe, A. Pace, B. Koller, P. G. Johnston, et al. BRCA1 Regulates the Interferon gamma -mediated Apoptotic Response J. Biol. Chem., July 12, 2002; 277(29): 26225 - 26232. [Abstract] [Full Text] [PDF]

				J.-i. Satoh and Y. Kuroda Differing effects of IFN{beta} vs IFN{gamma} in MS: Gene expression in cultured astrocytes Neurology, August 28, 2001; 57(4): 681 - 685. [Abstract] [Full Text] [PDF]

				B. T. Hummer, X.-L. Li, and B. A. Hassel Role for p53 in Gene Induction by Double-Stranded RNA J. Virol., August 15, 2001; 75(16): 7774 - 7777. [Abstract] [Full Text] [PDF]

				J. Bergeron, N. Benlimame, N. Zeng-Rong, D. Xiao, P. J. Scrivens, A. E. Koromilas, and M. A. Alaoui-Jamali Identification of the Interferon-inducible Double-Stranded RNA-dependent Protein Kinase as a Regulator of Cellular Response to Bulky Adducts Cancer Res., December 1, 2000; 60(24): 6800 - 6804. [Abstract] [Full Text]

				C. J. Grubbs, R. A. Lubet, A. T. Koki, K. M. Leahy, J. L. Masferrer, V. E. Steele, G. J. Kelloff, D. L. Hill, and K. Seibert Celecoxib Inhibits N-Butyl-N-(4-hydroxybutyl)-nitrosamine-induced Urinary Bladder Cancers in Male B6D2F1 Mice and Female Fischer-344 Rats Cancer Res., October 1, 2000; 60(20): 5599 - 5602. [Abstract] [Full Text]

				R. Lu, W.-C. Au, W.-S. Yeow, N. Hageman, and P. M. Pitha Regulation of the Promoter Activity of Interferon Regulatory Factor-7 Gene. ACTIVATION BY INTERFERON AND SILENCING BY HYPERMETHYLATION J. Biol. Chem., October 6, 2000; 275(41): 31805 - 31812. [Abstract] [Full Text] [PDF]

				M. J. Servant, B. ten Oever, C. LePage, L. Conti, S. Gessani, I. Julkunen, R. Lin, and J. Hiscott Identification of Distinct Signaling Pathways Leading to the Phosphorylation of Interferon Regulatory Factor 3 J. Biol. Chem., January 5, 2001; 276(1): 355 - 363. [Abstract] [Full Text] [PDF]