Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells

Min-Jung Kim, Kee-Ho Lee, Su-Jae Lee
FEBS Journal 2008, 275 (9): 2096-108
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"