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首页> 外文期刊>Molecular and Cellular Biology >Posttranscriptional Downregulation of c-IAP2 by the Ubiquitin Protein Ligase c-IAP1 In Vivo
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Posttranscriptional Downregulation of c-IAP2 by the Ubiquitin Protein Ligase c-IAP1 In Vivo

机译：泛素蛋白连接酶c-IAP1体内转录后c-IAP2的下调。

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Inhibitor of apoptosis proteins (IAPs) c-IAP1 and c-IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c-IAP1 and c-IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c-IAP1 in a physiologic setting, c-IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c-IAP1?/? mice do, however, express markedly elevated levels of c-IAP2 protein in the absence of increased c-IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-κB, resting and cytokine-induced NF-κB activation was not impaired in c-IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism.
机译：凋亡抑制蛋白（IAP）的抑制剂c-IAP1和c-IAP2被确定为肿瘤坏死因子受体2（TNFR2）信号复合物的一部分，并已被认为是肿瘤坏死因子α信号传导的中介。像所有包含RING域的IAP一样，c-IAP1和c-IAP2具有泛素蛋白连接酶（E3）活性。为了探索c-IAP1在生理环境中的功能，通过同源基因重组产生了c-IAP1缺陷小鼠。这些动物是有生存力的，对促凋亡的刺激没有明显的敏感性。然而，在不增加c-IAP2 mRNA的情况下，来自c-IAP1 α/？小鼠的细胞确实表达了明显升高的c-IAP2蛋白水平。与涉及c-IAPs激活NF-κB的报道相反，在c-IAP1缺陷型细胞中，静息和细胞因子诱导的NF-κB激活没有受到损害。用野生型和E3缺陷型c-IAP1进行的瞬时转染研究表明，c-IAP2是c-IAP1介导的泛素化和随后降解的直接靶标，这可由TRAF2的衔接子功能增强。因此，c-IAPs代表一对与TNFR相关的泛素蛋白连接酶，其中一个通过转录后和E3依赖性机制调节另一个的表达。

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