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Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells.
FEBS J. 2008 May; 275(9):2096-108.FJ

Abstract

Exposure of cells to ionizing radiation induces activation of multiple signaling pathways that play a critical role in controlling cell death. However, the basis for linkage between signaling pathways and the cell-death machinery in response to ionizing radiation remains unclear. Here we demonstrate that activation of c-Jun N-terminal kinase (JNK) is critical for amplification of mitochondrial cell death in human cervical cancer cells. Exposure of HeLa cells to radiation induced loss of mitochondrial membrane potential, release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria, and apoptotic cell death. Radiation also induced transcriptional upregulation of Fas, caspase-8 activation, Bax and Bak activation, and phosphorylation and downregulation of Bcl-2. Inhibition of caspase-8 attenuated Bax and Bak activation, but did not affect phosphorylation and downregulation of Bcl-2. Expression of a mutant form of Bcl-2 (S70A-Bcl-2) completely attenuated radiation-induced Bcl-2 downregulation. Interestingly, inhibition of JNK clearly attenuated radiation-induced Bax and Bak activation, and Bcl-2 phosphorylation as well as Fas expression. In addition, dominant-negative form of c-Jun inhibited radiation-induced Fas expression and Bax and Bak activation. These results indicate that the JNK-c-Jun pathway is required for the transcriptional upregulation of Fas and subsequent activation of Bax and Bak, and that JNK, but not c-Jun, is directly associated with phosphorylation and downregulation of Bcl-2 in response to ionizing radiation. These results suggest that ionizing radiation can utilize JNK for amplification of mitochondrial apoptotic cell death in human cervical cancer cells.

Authors+Show Affiliations

Laboratory of Molecular Biochemistry, Department of Chemistry, Hanyang University, Seoul, Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18373696

Citation

Kim, Min-Jung, et al. "Ionizing Radiation Utilizes c-Jun N-terminal Kinase for Amplification of Mitochondrial Apoptotic Cell Death in Human Cervical Cancer Cells." The FEBS Journal, vol. 275, no. 9, 2008, pp. 2096-108.
Kim MJ, Lee KH, Lee SJ. Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. FEBS J. 2008;275(9):2096-108.
Kim, M. J., Lee, K. H., & Lee, S. J. (2008). Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. The FEBS Journal, 275(9), 2096-108. https://doi.org/10.1111/j.1742-4658.2008.06363.x
Kim MJ, Lee KH, Lee SJ. Ionizing Radiation Utilizes c-Jun N-terminal Kinase for Amplification of Mitochondrial Apoptotic Cell Death in Human Cervical Cancer Cells. FEBS J. 2008;275(9):2096-108. PubMed PMID: 18373696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. AU - Kim,Min-Jung, AU - Lee,Kee-Ho, AU - Lee,Su-Jae, Y1 - 2008/03/28/ PY - 2008/4/1/pubmed PY - 2008/7/10/medline PY - 2008/4/1/entrez SP - 2096 EP - 108 JF - The FEBS journal JO - FEBS J VL - 275 IS - 9 N2 - Exposure of cells to ionizing radiation induces activation of multiple signaling pathways that play a critical role in controlling cell death. However, the basis for linkage between signaling pathways and the cell-death machinery in response to ionizing radiation remains unclear. Here we demonstrate that activation of c-Jun N-terminal kinase (JNK) is critical for amplification of mitochondrial cell death in human cervical cancer cells. Exposure of HeLa cells to radiation induced loss of mitochondrial membrane potential, release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria, and apoptotic cell death. Radiation also induced transcriptional upregulation of Fas, caspase-8 activation, Bax and Bak activation, and phosphorylation and downregulation of Bcl-2. Inhibition of caspase-8 attenuated Bax and Bak activation, but did not affect phosphorylation and downregulation of Bcl-2. Expression of a mutant form of Bcl-2 (S70A-Bcl-2) completely attenuated radiation-induced Bcl-2 downregulation. Interestingly, inhibition of JNK clearly attenuated radiation-induced Bax and Bak activation, and Bcl-2 phosphorylation as well as Fas expression. In addition, dominant-negative form of c-Jun inhibited radiation-induced Fas expression and Bax and Bak activation. These results indicate that the JNK-c-Jun pathway is required for the transcriptional upregulation of Fas and subsequent activation of Bax and Bak, and that JNK, but not c-Jun, is directly associated with phosphorylation and downregulation of Bcl-2 in response to ionizing radiation. These results suggest that ionizing radiation can utilize JNK for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. SN - 1742-464X UR - https://www.unboundmedicine.com/medline/citation/18373696/Ionizing_radiation_utilizes_c_Jun_N_terminal_kinase_for_amplification_of_mitochondrial_apoptotic_cell_death_in_human_cervical_cancer_cells_ L2 - https://doi.org/10.1111/j.1742-4658.2008.06363.x DB - PRIME DP - Unbound Medicine ER -