Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.
Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.
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DOI：
10.1016/j.exer.2016.02.011
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发表时间：
2017-03
影响因子：
3.4
通讯作者：
Taylor A
中科院分区：
文献类型：
--
作者：
Rowan S;Chang ML;Reznikov N;Taylor A
眼睛晶状体在组织中是独一无二的：它是透明的，不会形成肿瘤，并且其大部分细胞会降解其细胞器，包括细胞核。一个多世纪以来，晶状体纤维细胞去核（LFCD）一直是一个谜，但最近在阐明晶状体纤维细胞去核（LFCD）机制方面取得了相当大的进展。与有丝分裂期间细胞核的分解和重组相反，LFCD 是一个单向过程，最终导致纤维细胞核的破坏。 p27Kip1（细胞周期蛋白依赖性激酶抑制剂）在 LFC 形成过程中在最外层皮质、内层皮质、新生细胞器自由区中上调，而 p27Kip1 则被降解，显着激活细胞周期蛋白依赖性激酶 1 (Cdk1)。该过程导致核纤层蛋白的磷酸化、核膜的解离以及溶酶体的进入，释放 DNaseIIβ (DLAD) 以裂解染色质。多种细胞途径，包括泛素蛋白酶体系统和未折叠蛋白反应，集中于 p27Kip1 的翻译后调节。损害这些通路的突变与先天性白内障和 LFCD 丧失有关。这些发现突出了镜头中的新调控节点，并表明我们已经接近了解这一令人着迷的终末分化过程。这些知识可能会提供一种新的方法来应对包括癌症在内的增殖性疾病。
The eye lens is unique among tissues: it is transparent, does not form tumors, and the majority of its cells degrade their organelles, including their cell nuclei. A mystery for over a century, there has been considerable recent progress in elucidating mechanisms of lens fiber cell denucleation (LFCD). In contrast to the disassembly and reassembly of the cell nucleus during mitosis, LFCD is a unidirectional process that culminates in destruction of the fiber cell nucleus. Whereas p27Kip1, the cyclin-dependent kinase inhibitor, is upregulated during formation of LFC in the outermost cortex, in the inner cortex, in the nascent organelle free zone, p27Kip1 is degraded, markedly activating cyclin-dependent kinase 1 (Cdk1). This process results in phosphorylation of nuclear Lamins, dissociation of the nuclear membrane, and entry of lysosomes that liberate DNaseIIβ (DLAD) to cleave chromatin. Multiple cellular pathways, including the ubiquitin proteasome system and the unfolded protein response, converge on post-translational regulation of p27Kip1. Mutations that impair these pathways are associated with congenital cataracts and loss of LFCD. These findings highlight new regulatory nodes in the lens and suggest that we are close to understanding this fascinating terminal differentiation process. Such knowledge may offer a new means to confront proliferative diseases including cancer.