Increase of RhoB in gamma-radiation-induced apoptosis is regulated by c-Jun N-terminal kinase in Jurkat T cells.
The Ras-related small GTP-binding protein RhoB is known to be a pro-apoptotic protein and immediate-early inducible by genotoxic stresses. In addition, JNK activation is known to function in gamma-radiation-induced apoptosis. However, it is unclear how JNK activation and gamma-radiation-dependent RhoB induction are related. Here we verified the relationship between JNK activation and RhoB induction. RhoB induction by gamma-radiation occurred at the transcriptional level and transcriptional activation of RhoB was concomitant with an increase in RhoB protein. gamma-Radiation-induced RhoB expression was markedly attenuated by pretreatment with a JNK-specific inhibitor, SP600125, but not by a p38 MAPK inhibitor, SB203580. Inhibition of JNK caused a decrease in early apoptotic cell death that correlated with RhoB expression. However, PI3K inhibition had no significant effects, indicating that the AKT survival pathway was not involved. The siRNA knockdown of JNK resulted in a decrease in RhoB expression and the siRNA knockdown of RhoB restored cell growth even in the gamma-irradiated cells. These results suggest that RhoB regulation involves the JNK pathway and contributes to the early apoptotic response of Jurkat T cells to gamma-radiation.
Kim
Chun-Ho
CH
Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706, Republic of Korea.
Won
Misun
M
Choi
Chung-Hae
CH
Ahn
Jiwon
J
Kim
Bo-Kyung
BK
Song
Kyung-Bin
KB
Kang
Chang-Mo
CM
Chung
Kyung-Sook
KS
D017209:Apoptosis; D005720:Gamma Rays; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology / Q000528:radiation effects*; D014158:Transcription, Genetic; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
D034741:RNA, Small Interfering; D048031:JNK Mitogen-Activated Protein Kinases; D020743:rhoB GTP-Binding Protein