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Necdin: A purposive integrator of molecular interaction networks for mammalian neuron vitality
Genes to Cells ( IF 1.3 ) Pub Date : 2021-08-02 , DOI: 10.1111/gtc.12884
Kazuaki Yoshikawa 1
Affiliation  

Necdin was originally found in 1991 as a hypothetical protein encoded by a neural differentiation-specific gene transcript in murine embryonal carcinoma cells. Virtually all postmitotic neurons and their precursor cells express the necdin gene (Ndn) during neuronal development. Necdin mRNA is expressed only from the paternal allele through genomic imprinting, a placental mammal-specific epigenetic mechanism. Necdin and its homologous MAGE (melanoma antigen) family, which have evolved presumedly from a subcomplex component of the SMC5/6 complex, are expressed exclusively in placental mammals. Paternal Ndn-mutated mice totally lack necdin expression and exhibit various types of neuronal abnormalities throughout the nervous system. Ndn-null neurons are vulnerable to detrimental stresses such as DNA damage. Necdin also suppresses both proliferation and apoptosis of neural stem/progenitor cells. Functional analyses using Ndn-manipulated cells reveal that necdin consistently exerts antimitotic, anti-apoptotic and prosurvival effects. Necdin interacts directly with a number of regulatory proteins including E2F1, p53, neurotrophin receptors, Sirt1 and PGC-1α, which serve as major hubs of protein–protein interaction networks for mitosis, apoptosis, differentiation, neuroprotection and energy homeostasis. This review focuses on necdin as a pleiotropic protein that integrates molecular interaction networks to promote neuronal vitality in modern placental mammals.

中文翻译:

Necdin:哺乳动物神经元活力的分子相互作用网络的有目的的整合者

Necdin 最初于 1991 年被发现是一种假设的蛋白质,由鼠胚胎癌细胞中的神经分化特异性基因转录物编码。几乎所有的有丝分裂后神经元及其前体细胞在神经元发育过程中都表达 necdin 基因 (Ndn)。Necdin mRNA 仅通过基因组印记(一种胎盘哺乳动物特异性表观遗传机制)从父系等位基因中表达。Necdin 及其同源 MAGE(黑色素瘤抗原)家族,推测是从 SMC5/6 复合体的亚复合体成分进化而来的,仅在胎盘哺乳动物中表达。父系 Ndn 突变小鼠完全缺乏 necdin 表达,并在整个神经系统中表现出各种类型的神经元异常。Ndn-null 神经元容易受到 DNA 损伤等有害压力的影响。Necdin 还抑制神经干/祖细胞的增殖和凋亡。使用 Ndn 操作的细胞的功能分析表明,necdin 始终发挥抗有丝分裂、抗凋亡和促生存作用。Necdin 直接与许多调节蛋白相互作用,包括 E2F1、p53、神经营养因子受体、Sirt1 和 PGC-1α,它们是有丝分裂、细胞凋亡、分化、神经保护和能量稳态的蛋白质-蛋白质相互作用网络的主要枢纽。这篇综述着重于 necdin 作为一种多效性蛋白,它整合了分子相互作用网络以促进现代胎盘哺乳动物的神经元活力。Necdin 直接与许多调节蛋白相互作用,包括 E2F1、p53、神经营养因子受体、Sirt1 和 PGC-1α,它们是有丝分裂、细胞凋亡、分化、神经保护和能量稳态的蛋白质-蛋白质相互作用网络的主要枢纽。这篇综述着重于 necdin 作为一种多效性蛋白,它整合了分子相互作用网络以促进现代胎盘哺乳动物的神经元活力。Necdin 直接与许多调节蛋白相互作用,包括 E2F1、p53、神经营养因子受体、Sirt1 和 PGC-1α,它们是有丝分裂、细胞凋亡、分化、神经保护和能量稳态的蛋白质-蛋白质相互作用网络的主要枢纽。这篇综述着重于 necdin 作为一种多效性蛋白,它整合了分子相互作用网络以促进现代胎盘哺乳动物的神经元活力。
更新日期:2021-09-09
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