NPM-RAR binding to TRADD selectively inhibits caspase activation, while allowing activation of NFκB and JNK.
NPM-RAR binding to TRADD selectively inhibits caspase activation, while allowing activation of NFκB and JNK.
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DOI：
10.3109/10428194.2015.1023799
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发表时间：
2015
影响因子：
2.6
通讯作者：
Redner RL
中科院分区：
文献类型：
--
作者：
Chattopadhyay A;Abecassis I;Redner RL
急性早幼粒细胞白血病(APL)的t(5；17)变异体表达核磷蛋白(NPM)与维甲酸受体α(RARA)的融合。我们之前已经证明NPM-RAR是肿瘤坏死因子受体I型相关死亡结构域蛋白Tradd的结合伙伴。肿瘤坏死因子与其受体TnFR1结合，诱导TradD的募集，随后一系列蛋白的募集最终激活Caspase3、NFκB和JNK.我们以前已经证明，NPM-RAR与Tradd的相互作用可以阻断caspase 3、caspase 8、PARP裂解的TNF激活，最终导致细胞凋亡。我们现在报道，NPM-RAR的表达允许肿瘤坏死因子激活NFJNK B和κ。我们认为，抑制肿瘤坏死因子活化的细胞凋亡，同时保留肿瘤坏死因子激活的核因子κB和JNK途径，刺激细胞的生长和存活，是一个新的机制，通过它促进白血病的表型发展。
The t(5;17) variant of acute promeylocytic leukemia (APL) expresses a fusion of nucleophosmin (NPM) with the retinoic acid receptor alpha (RARA). We have previously shown that NPM-RAR is a binding partner of the tumor necrosis factor receptor type-I –associated DEATH domain protein TRADD. Binding of TNF to its receptor, TNFR1, induces recruitment of TRADD, and subsequent recruitment of a cascade of proteins that ultimate activate caspase 3, NFκB , and JNK. We have previously shown that NPM-RAR interaction with TRADD blocks TNF activation of caspase 3, caspase 8, PARP cleavage, and ultimately, apoptosis. We now report that NPM-RAR expression is permissive for TNF activation of NFκB and JNK. We propose that inhibition of TNF activation of apoptosis, while preserving TNF activation of NFκB and JNK pathways that stimulate cell growth and survival, represents a novel mechanism through which NPM-RAR contributes to development of the leukemic phenotype.