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【编译】衔接蛋白TRADD可激活细胞核和细胞质中的
The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm
来源
Cell Death and Differentiation (2005) 12, 473−481. doi: 10.1038/sj.cdd.4401578 Published online 11 March 2005
Published online 11 March 2005
http://www.nature.com/cdd/journal/v12/n5/abs/4401578a.html
摘要原文
TNFR1 associated death domain protein (TRADD) contains an N-terminal TRAF binding domain and a C-terminal death domain along with nuclear import and export sequences that cause shuttling between the cytoplasm and nucleus. The death domain of TRADD contains the nuclear import sequence and expression of the core death domain (nuclear TRADD) results in exclusive nuclear localization and activation of a distinct apoptotic pathway. Cytoplasmic TRADD activates apoptosis through Fas-associated death domain protein (FADD) and caspase-8 activation that was blocked by caspase inhibitors or dominant-negative FADD. These inhibitors did not inhibit death induced by nuclear TRADD, which could only be inhibited by combining caspase inhibitors and a serine protease inhibitor. The pathway activated by nuclear TRADD requires caspase-9 catalytic activity. However, apoptosis activating factor deficiency confers only partial protection from death. This pathway represents an alternate means by which TRADD can regulate cell death independently of FADD and caspase-8 that occurs from the nucleus rather than the cytoplasm.
编译
TNFR1相关死亡结构域蛋白(TRADD) 包含有一个N末端TRAF结合区域和一个C末端死亡结构域，这些结构域还带有核输入输出序列，使得能够在细胞核和细胞质之间穿梭运动。TRADD的死亡结构域包含有核输入序列，核死亡结构域(nuclear TRADD) 的表达可导致特殊的核定位和特异性细胞凋亡途径的激活。胞质TRADD可通过Fas相关死亡结构域蛋白(FADD)和caspase-8 的活化激活细胞凋亡。而caspase抑制因子或显性负相FADD可以阻断FADD 和caspase-8的活化。但是这些抑制因子并不能抑制由核TRADD诱导的死亡，只有结合性caspase抑制剂和丝氨酸蛋白酶抑制剂才能抑制这种死亡。由核TRADD激活的途径需要caspase-9催化活性。然而，细胞凋亡活化因子的缺乏仅能保护部分细胞免于死亡。这个途径阐明了另一种方法。通过这种方法TRADD能够不依赖FADD和caspase-8而调节细胞死亡，这种细胞死亡发生在细胞核而不是在细胞质。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-03-06 05:21
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