Collapsin response mediator protein 3 deacetylates histone H4 to mediate nuclear condensation and neuronal death.
Collapsin response mediator protein 3 deacetylates histone H4 to mediate nuclear condensation and neuronal death.
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DOI：
10.1038/srep01350
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发表时间：
2013
影响因子：
4.6
通讯作者：
Zhou, Lei
中科院分区：
文献类型：
--
作者：
Hou, Sheng T.;Jiang, Susan X.;Aylsworth, Amy;Cooke, Matthew;Zhou, Lei
CRMP蛋白在脑信号蛋白介导的神经突起生长、神经元分化和死亡过程中起着重要的调节作用。尽管与肝脏二氢嘧啶酶具有高度的结构和序列相似性，但纯化的啮齿动物脑CRMP不水解二氢嘧啶酶底物。在这里，我们发现小鼠CRMP 3具有强大的组蛋白H4脱乙酰酶活性。在兴奋性毒性诱导的小鼠神经元死亡过程中，钙蛋白酶切割的N-末端截短的CRMP 3通过组蛋白H4的脱乙酰化进行核转位以引起核浓缩。CRMP 3介导的H4脱乙酰化导致E2 F1基因转录的去抑制和E2 F1依赖性神经元死亡。这些研究揭示了CRMP 3在神经元死亡中的新机制。结合先前充分建立的文献，即组蛋白脱乙酰酶活性的抑制提供神经保护，我们设想CRMP 3的抑制可能代表针对兴奋性毒性诱导的神经元死亡的新的治疗方法。
CRMP proteins play critical regulatory roles during semaphorin-mediated neurite outgrowth, neuronal differentiation and death. Albeit having a high degree of structure and sequence resemblance to that of liver dihydropyrimidinase, purified rodent brain CRMPs do not hydrolyze dihydropyrimidinase substrates. Here we found that mouse CRMP3 has robust histone H4 deacetylase activity. During excitotoxicity-induced mouse neuronal death, calpain-cleaved, N-terminally truncated CRMP3 undergoes nuclear translocation to cause nuclear condensation through deacetylation of histone H4. CRMP3-mediated deacetylation of H4 leads to de-repression of the E2F1 gene transcription and E2F1-dependent neuronal death. These studies revealed a novel mechanism of CRMP3 in neuronal death. Together with previous well established bodies of literature that inhibition of histone deacetylase activity provides neuroprotection, we envisage that inhibition of CRMP3 may represent a novel therapeutic approach towards excitotoxicity-induced neuronal death.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
64.8
作者：
GOSHIMA, Y;NAKAMURA, F;STRITTMATTER, SM
通讯作者：
STRITTMATTER, SM
影响因子：
2.7
作者：
HEDGECOCK, EM;CULOTTI, JG;PERKINS, LA
通讯作者：
PERKINS, LA
影响因子：
5.3
作者：
Hou, ST;Jiang, SX;Kappler, J
通讯作者：
Kappler, J
影响因子：
2.5
作者：
Hou, ST;Cowan, E;MacManus, JP
通讯作者：
MacManus, JP