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首页> 外文期刊>EMBO Journal >INDUCTION OF APOPTOSIS BY THE TRANSCRIPTION FACTOR C-JUN [Review]
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INDUCTION OF APOPTOSIS BY THE TRANSCRIPTION FACTOR C-JUN [Review]

机译：转录因子诱导细胞凋亡C-JUN(审查)

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摘要

c-Jun, a signal-transducing transcription factor of the AP-1 family, normally implicated in cell cycle progression, differentiation and cell transformation, recently has also been linked to apoptosis, To explore further the functional roles of c-Jun, a conditional allele was generated by fusion of c-Jun with the hormone-binding domain of the human estrogen receptor (ER). Here we demonstrate that increased c-Jun activity is sufficient to trigger apoptotic cell death in NIH 3T3 fibroblasts. c-Jun-induced apoptosis is evident at high serum levels, but is enhanced further in factor-deprived fibroblasts. Furthermore, apoptosis by c-Jun is not accompanied by an increase in DNA synthesis. Constitutive overexpression of the apoptosis inhibitor protein Bcl-2 delays the c-Jun-mediated cell death, The regions of c-Jun necessary for apoptosis induction include the amino-terminal transactivation and the carboxyterminal leucine zipper domain, suggesting that c-Jun may activate cell death by acting as a transcriptional regulator. We further show that alpha-fodrin, a substrate of the interleukin 1 beta-converting enzyme (ICE) and CED-3 family of cysteine proteases, becomes proteolytically cleaved in cells. undergoing cell death by increased c-Jun activity. Moreover, cell-permeable irreversible peptide inhibitors of the ICE/CED-3 family of cysteine proteases prevented the cell death. [References: 118]
机译：c-Jun signal-transducing转录因子AP-1家族,通常涉及细胞循环发展,分化和细胞转换,最近也有关细胞凋亡,探讨进一步的功能c-Jun的角色,有条件的等位基因由c-Jun的融合hormone-binding域人类的雌激素受体(ER)。c-Jun活动足以引发凋亡NIH 3 t3成纤维细胞的细胞死亡。在高血清细胞凋亡是显而易见的,但是在factor-deprived成纤维细胞进一步增强。此外,由c-Jun不是细胞凋亡伴随着DNA合成的增加。本构超表达的细胞凋亡抑制剂c-Jun-mediated bcl - 2蛋白的延迟细胞死亡,c-Jun必要的地区细胞凋亡诱导包括伴transactivation carboxyterminal亮氨酸拉链域,这表明c-Jun可能激活细胞死亡作为转录监管机构。白介素1 beta-converting的衬底酶(ICE)和CED-3半胱氨酸的家庭蛋白酶,成为proteolytically裂解细胞。活动。肽抑制剂的冰/ CED-3家庭半胱氨酸蛋白酶阻止了细胞的死亡。(引用:118)

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