高等哺乳动物LEM结构域蛋白家族的研究进展

Structural and functional studies of mammalian LEM-domain proteins

在高等动物细胞开放式有丝分裂过程中,细胞核膜会发生高度有序的周期性去组装和装配的动态变化。近年的研究结果表明是LEM家族蛋白成员通过与BAF因子相互作用介导了内核膜、核纤层蛋白以及染色体之间的相互作用。LEM蛋白、核纤层蛋白以及BAF因子直接相互作用形成的三元复合体在结构与功能上是相互依赖的,在此结构与功能上组成的网络体系是形成细胞核的一些基本生物学过程的重要条件。该复合体在调控有丝分裂M期后期和末期染色体的正常分离、有丝分裂后核膜的重组装,细胞分裂间期细胞核及核膜形态维持,调控DNA复制和DNA损伤修复,调节基因表达和信号通路以及逆转录病毒感染等方面发挥着重要的生物学功能。并且LEM蛋白相关基因的异常对核纤层疾病和肿瘤的发生发展具有重要的影响。文章主要针对LEM蛋白家族成员的结构以及功能研究进展进行了详细的综述。

During the process of open mitosis in higher eukaryotic cells, the nuclear envelope （NE） is disassembled and reassembled with highly organized and periodical dynamic morphological changes. Recent studies demonstrated that LEM-domain protein family mediates interactions among inner nuclear membrane, nuclear lamina protein and chromatin by interacting with barrier-to-autointegration-factor （BAF）. The structure and function of the ternary complex formed by LEM-domain protein, nuclear lamina protein and BAF are dependent on each other. Moreover, the network formation based on this structure and function is critical for the development of basic biological processes of nuclear, and it plays important roles in chromatin separation in late metaphase and anapbase, NE reassembly after mitosis, morphological maintenance of nuclear and NE in interphase, regulation of DNA replication and DNA damage repair, regulation of gene expression and signaling pathway, and infection of retrovirus. Mutations in genes encoding LEM family proteins have important impacts on development and progression of laminopathic dis- eases and tumorigenesis. This review provides a detailed summary of structural and functional studies of the LEM family proteins.