TNFR80-dependent enhancement of TNFR60-induced cell death is mediated by TNFR-associated factor 2 and is specific for TNFR60.
TNFR80-dependent enhancement of TNFR60-induced cell death is mediated by TNFR-associated factor 2 and is specific for TNFR60.
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TNFR60 诱导的细胞死亡的 TNFR80 依赖性增强是由 TNFR 相关因子 2 介导的，并且对 TNFR60 具有特异性。
作者：
Tilo Weiss;M. Grell;K. Siemienski;Frank Mühlenbeck;H. Dürkop;K. Pfizenmaier;P. Scheurich;Harald Wajant
TNFR 80的共刺激可以强烈增强TNFR 60诱导的细胞死亡。在这项研究中，我们表明，这种增强是TNFR 60的选择性，既不是TNF相关的凋亡诱导配体/载脂蛋白2配体，载脂蛋白1/Fas，神经酰胺，也不是柔红霉素介导的细胞死亡的影响，共刺激TNFR 80。我们进一步证明，肿瘤坏死因子相关因子2（TRAF 2）是至关重要的参与负和正调节肿瘤坏死因子诱导的细胞死亡。TRAF 2和TRAF 2突变体的过表达，缺乏核因子-kappaB激活，选择性脱敏和增强，分别在HeLa细胞中TNFR 60诱导的细胞死亡。然而，在共刺激TNFR 80（其通过TRAF 2介导核因子-κ B和c-Jun氨基末端激酶的活化）后，TNF诱导的细胞死亡在亲本和TRAF 2转染的细胞中显著增强，但在TRAF 2（87-501）转染的细胞中不增强。这些数据指出TRAF 2在凋亡TNFR串扰中的关键作用，由此TNFR 60诱导的细胞死亡的TNFR 80依赖性增强是由于TNFR 80介导的TRAF 2功能的负调节。通过分析TNFR 80预刺激后TNFR 60对c-Jun氨基末端激酶活化的影响，独立证实了对TRAF 2功能的干扰。我们提出，凋亡TNFR的串扰是基于TNFR 80介导的废除由TNFR 60启动的抗凋亡TRAF 2依赖性信号通路，但不是Apo 1/Fas或凋亡TNF相关的凋亡诱导配体受体。
Costimulation of TNFR80 can strongly enhance TNFR60-induced cell death. In this study, we show that this enhancement is TNFR60 selective, as neither TNF-related apoptosis-inducing ligand/Apo2 ligand-, Apo1/Fas-, ceramide-, nor daunorubicin-mediated cell death was affected by costimulation of TNFR80. We further demonstrate that TNFR-associated factor 2 (TRAF2) is critically involved in both negative and positive regulation of TNF-induced cell death. Overexpression of TRAF2 and of a TRAF2 mutant, deficient in nuclear factor-kappaB activation, selectively desensitized and enhanced, respectively, TNFR60-induced cell death in HeLa cells. However, upon costimulation of TNFR80, which mediates activation of nuclear factor-kappaB and the c-Jun amino-terminal kinase via TRAF2, TNF-induced cell death is drastically enhanced in parental and TRAF2-transfected, but not in TRAF2 (87-501)-transfected cells. These data point to a critical role of TRAF2 in the apoptotic TNFR cross talk, whereby the TNFR80-dependent enhancement of TNFR60-induced cell death is due to TNFR80-mediated negative regulation of TRAF2 function(s). An interference with TRAF2 function was confirmed independently by analysis of c-Jun amino-terminal kinase activation via TNFR60 upon prestimulation of TNFR80. We propose that the apoptotic TNFR cross talk is based on TNFR80-mediated abrogation of antiapoptotic TRAF2-dependent signaling pathways initiated by TNFR60, but not Apo1/Fas or the apoptotic TNF-related apoptosis-inducing ligand receptors.
DOI：
10.1073/pnas.92.18.8443
发表时间：
1995-08
影响因子：
11.1
作者：
C. Tepper;S. Jayadev;Bin Liu;A. Bielawska;R. A. Wolff;S. Yonehara;Y. Hannun;M. Seldin
通讯作者：
C. Tepper;S. Jayadev;Bin Liu;A. Bielawska;R. A. Wolff;S. Yonehara;Y. Hannun;M. Seldin
影响因子：
10.5
作者：
Duckett, CS;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
56.9
作者：
Yeh, WC;de la Pompa, JL;Mak, TW
通讯作者：
Mak, TW