The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation - Duration of JNK activation may determine cell death and proliferation
The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation - Duration of JNK activation may determine cell death and proliferation
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DOI：
10.1074/jbc.271.50.31929
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发表时间：
1996-12-13
影响因子：
4.8
通讯作者：
Tan, TH
中科院分区：
文献类型：
--
作者：
Chen, YR;Wang, XP;Tan, TH
c-Jun N-末端激酶（JNK）参与细胞对促有丝分裂刺激、环境应激和凋亡剂的应答。JNK与其他信号通路整合并调节多种细胞事件的机制尚不清楚。我们发现JNK，而不是p38-丝裂原活化蛋白激酶（MAPK）或细胞外信号调节激酶2，持续激活γ辐射，UV-C，抗Fas治疗诱导的细胞凋亡。JNK激活与UV-C和γ辐射诱导的细胞凋亡之间存在直接相关性;然而，JNK诱导与Fas信号转导诱导的细胞凋亡之间没有很好的相关性。激活JNK 1的过表达引起转染细胞中的细胞死亡，并且MAPK激酶1或JNK 1的显性负突变体（但不是p38-MAPK或c-Raf的显性负突变体）的表达阻止UV-C和γ辐射诱导的细胞死亡。JNK在T细胞活化和凋亡中的诱导作用分别通过不同的活化模式（瞬时与持续）来区分。酪氨酸磷酸酶抑制剂（原钒酸钠）和T细胞活化信号（佛波醇12-肉豆蔻酸酯13-乙酸酯加离子霉素）的共同治疗延长了JNK诱导，随后是T细胞凋亡。我们的数据揭示了JNK通路在辐射诱导的细胞凋亡中的需求，并暗示了JNK激活的持续时间在决定细胞命运中的重要性。
c-Jun N-terminal kinases (JNKs) participate in cellular responses to mitogenic stimuli, environmental stresses, and apoptotic agents. The mechanisms by which JNK integrates with other signaling pathways and regulates the diverse cellular events are unclear. We found JNK, but not p38-mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase 2, to be persistently activated in apoptosis induced by gamma radiation, UV-C, and anti-Fas treatment. Direct correlation was found between JNK activation and apoptosis induced by UV-C and gamma radiation; however, JNK induction and apoptosis induced by Fas signaling were not well correlated. Overexpression of activated JNK1 caused cell death in transfected cells, and the expression of a dominant-negative mutant of MAPK kinase 1 or JNK1 (but not a dominant-negative mutant of p38-MAPK or c-Raf) prevented the UV-C- and gamma radiation-induced cell death. The inductions of JNK in T-cell activation and apoptosis were distinguished by the different activation patterns, transient versus persistent, respectively. Co-treatment with a tyrosine phosphatase inhibitor (sodium orthovanadate) and T-cell activation signals (phorbol 12-myristate 13-acetate plus ionomycin) prolonged JNK induction, followed by T-cell apoptosis. Our data revealed the requirement of the JNK pathway in radiation-induced apoptosis and implicated the importance of the duration of JNK activation in determining the cell fates.