Translocation of TRAF proteins regulates apoptotic threshold of cells
Translocation of TRAF proteins regulates apoptotic threshold of cells
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DOI：
10.1006/bbrc.2000.2873
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发表时间：
2000-06-16
影响因子：
3.1
通讯作者：
Thompson, CB
中科院分区：
文献类型：
--
作者：
Arch, RH;Gedrich, RW;Thompson, CB
肿瘤坏死因子（TNF）受体相关因子（TRAFs）参与由TNF受体（TNFR）家族成员和其他细胞表面蛋白触发的信号传导途径。在募集到受体后，TRAF启动诱导下游事件的多蛋白复合物的形成，例如转录因子核因子κ B（NF-κ B）的易位和c-Sun N-末端激酶（JNK）的活化。这些复合物中的几种蛋白质在细胞凋亡的调节中起重要作用。然而，含有TRAF的复合物一旦响应于受体多聚化而组装，其命运尚不清楚。在这份报告中，我们证明了TNFR家族成员的交联或TRAF 2与细胞质蛋白A20的相互作用导致TRAF 2的细胞内易位。这种重新分配导致TRAF 2细胞质库的耗尽。可溶性和不溶性TRAF 2之间的比例决定了细胞对TNF-α诱导的凋亡的敏感性，并可能在限制进一步的TRAF依赖性信号转导中发挥重要作用。(C)北京大学出版社.
Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are involved in signaling pathways triggered by members of the TNF receptor (TNFR) family and other cell surface proteins. After recruitment to a receptor, TRAFs initiate formation of multiprotein complexes that induce downstream events, such as translocation of transcription factor nuclear factor kappa B (NF-kappa B) and activation of c-Sun N-terminal kinase (JNK). Several proteins in these complexes play important roles in regulation of apoptosis. However, the fate of TRAF-containing complexes once assembled in response to receptor multimerization is not understood. In this report, we demonstrate that crosslinking of TNFR family members or interaction of TRAF2 with the cytoplasmic protein A20 leads to intracellular translocation of TRAF2. This redistribution leads to depletion of the cytoplasmic pool of TRAF2. The ratio between soluble and insoluble TRAF2 determines the sensitivity of cells to TNF-alpha-induced apoptosis and may play an important role in limiting further TRAF-dependent signal transduction. (C) 2000 Academic Press.