The limited role of NH2-terminal c-Jun phosphorylation in neuronal apoptosis
The limited role of NH2-terminal c-Jun phosphorylation in neuronal apoptosis
复制标题
NH2末端c-Jun磷酸化在神经细胞凋亡中的有限作用
DOI：
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发表时间：
2005
影响因子：
7.8
通讯作者：
Eugene M. Johnson
中科院分区：
文献类型：
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作者：
C. Besirli;E. Wagner;Eugene M. Johnson
c-Jun在许多神经元死亡范例中被诱导。c-Jun调节的关键步骤涉及位于NH 2-末端反式激活结构域的Ser 63/Ser 73的磷酸化。为了确定这种磷酸化对神经元凋亡的重要性，我们分析了携带缺乏Ser 63/Ser 73磷酸化位点（jun aa）的突变c-Jun基因的小鼠的交感神经元。在jun aa/aa神经元中，营养因子剥夺或DNA损伤诱导的死亡显著延迟。神经元c-Jun诱导仅被部分抑制，表明Ser 63/73的磷酸化不是c-Jun激活所必需的。促凋亡蛋白BH 3的诱导，Bim和Bbc 3/Bbc 3，在突变神经元的神经元凋亡过程中延迟。这些结果表明，NH 2-末端c-Jun磷酸化是重要的，但不是必需的，诱导促凋亡基因和神经元凋亡。因此，额外的JNK底物可能是神经元死亡的关键。作为潜在的介体，我们确定了其他的核MLK/JNK底物，包括核孔复合物的Nup 214亚基。
c-Jun is induced in many neuronal death paradigms. A critical step in c-Jun regulation involves phosphorylation of Ser63/Ser73 located in the NH2-terminal transactivation domain. To determine the importance of this phosphorylation for neuronal apoptosis, we analyzed the sympathetic neurons of mice carrying a mutant c-Jun gene that lacks Ser63/Ser73 phosphorylation sites (jun aa). Trophic factor–deprivation or DNA damage–induced death was significantly delayed in jun aa/aa neurons. Neuronal c-Jun induction was only partially inhibited, demonstrating that phosphorylation of Ser63/73 is not required for c-Jun activation. The inductions of proapoptotic BH3-only proteins, Bim and PUMA/Bbc3, were delayed during neuronal apoptosis in mutant neurons. These results demonstrate that NH2-terminal c-Jun phosphorylation is important, but not necessary, for the induction of proapoptotic genes and neuronal apoptosis. Thus, additional JNK substrates may be critical for neuronal death. As potential mediators, we identified additional nuclear MLK/JNK substrates, including Nup214 subunit of the nuclear pore complex.
影响因子：
16
作者：
Yu, J;Zhang, L;Vogelstein, B
通讯作者：
Vogelstein, B
DOI：
10.1074/jbc.m104073200
发表时间：
2001-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Charles A. Harris;Eugene M. Johnson
通讯作者：
Charles A. Harris;Eugene M. Johnson