Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression.
Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression.
复制标题
肿瘤坏死因子 α 刺激引起的 Caspase-8 依赖性 HER-2 裂解可通过 c-FLIP-L 表达被核因子 kappaB 抵消。
作者：
V. Benoit;A. Chariot;L. Delacroix;V. Deregowski;N. Jacobs;M. Merville;V. Bours
癌蛋白HER-2/neu是一种生存因子，其过度表达与乳腺癌患者的预后不良有关。我们报道HER-2是caspase-8的新底物，肿瘤坏死因子α(TNF-α)刺激导致核因子kappaB(NFkappaB)激活缺陷的MCF7A/Z乳腺癌细胞中caspase-8依赖的HER-2早期裂解。我们表明，抗凋亡转录因子NFkappaB通过诱导caspase-8抑制剂c-flip来抵消这种切割。我们的结果还表明，这种HER-2裂解参与了肿瘤坏死因子-α诱导的细胞凋亡途径，因为不能裂解的HER-2的异位表达保护NFkappaB缺陷细胞免受肿瘤坏死因子-α介导的细胞死亡。因此，我们提出了一个原始的模型，在该模型中，NFkappaB通过对抗肿瘤坏死因子-α触发的HER-2生存因子的切割而发挥新的抗凋亡功能。
The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and that tumor necrosis factor alpha (TNF-alpha) stimulation leads to an early caspase-8-dependent HER-2 cleavage in MCF7 A/Z breast adenocarcinoma cells defective for nuclear factor kappaB (NFkappaB) activation. We show that the antiapoptotic transcription factor NFkappaB counteracts this cleavage through induction of the caspase-8 inhibitor c-FLIP. Our results also demonstrate that this HER-2 cleavage contributes to the TNF-alpha-induced apoptosis pathway because ectopic expression of an uncleavable HER-2 protects NFkappaB-defective cells against TNF-alpha-mediated cell death. Therefore, we propose an original model in which NFkappaB exerts a new antiapoptotic function by counteracting TNF-alpha-triggered cleavage of the HER-2 survival factor.
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影响因子：
16
作者：
Yu, DH;Tian, J;Hung, MC
通讯作者：
Hung, MC
影响因子：
11.2
作者：
M. Press;M. Pike;V. Chazin;G. Hung;J. Udove;Mitchell Markowicz;J. Danyluk;W. Godolphin;M. Sliwkowski
通讯作者：
M. Press;M. Pike;V. Chazin;G. Hung;J. Udove;Mitchell Markowicz;J. Danyluk;W. Godolphin;M. Sliwkowski
DOI：
10.1016/s0021-9258(19)37138-8
发表时间：
1992-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Krikos;C. D. Laherty;V. Dixit
通讯作者：
A. Krikos;C. D. Laherty;V. Dixit
影响因子：
11.2
作者：
A. Berchuck;R. Whitaker;G. Olt;J. Soper;D. Clarke‐Pearson;A. Kamel;A. Kamel;R. Bast;B. Kerns;R. Kinney;R. Dodge;P. Marks;S. McKenzie;S. Yin
通讯作者：
A. Berchuck;R. Whitaker;G. Olt;J. Soper;D. Clarke‐Pearson;A. Kamel;A. Kamel;R. Bast;B. Kerns;R. Kinney;R. Dodge;P. Marks;S. McKenzie;S. Yin
影响因子：
8
作者：
X. Zhang;E. Silva;D. Gershenson;M. Hung
通讯作者：
X. Zhang;E. Silva;D. Gershenson;M. Hung