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细胞内稳态相关核纤层蛋白及相关输入信号概述

Overview of cellular homeostasis-associated nuclear envelope lamins and associated input signals.

作者信息

Kim Hyeong Jae, Lee Peter C W, Hong Jeong Hee

机构信息

Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.

Lung Cancer Research Center, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

出版信息

Front Cell Dev Biol. 2023 May 12;11:1173514. doi: 10.3389/fcell.2023.1173514. eCollection 2023.

Abstract

With the discovery of the role of the nuclear envelope protein lamin in human genetic diseases, further diverse roles of lamins have been elucidated. The roles of lamins have been addressed in cellular homeostasis including gene regulation, cell cycle, cellular senescence, adipogenesis, bone remodeling as well as modulation of cancer biology. Features of laminopathies line with oxidative stress-associated cellular senescence, differentiation, and longevity and share with downstream of aging-oxidative stress. Thus, in this review, we highlighted various roles of lamin as key molecule of nuclear maintenance, specially lamin-A/C, and mutated gene clearly reveal aging-related genetic phenotypes, such as enhanced differentiation, adipogenesis, and osteoporosis. The modulatory roles of lamin-A/C in stem cell differentiation, skin, cardiac regulation, and oncology have also been elucidated. In addition to recent advances in laminopathies, we highlighted for the first kinase-dependent nuclear lamin biology and recently developed modulatory mechanisms or effector signals of lamin regulation. Advanced knowledge of the lamin-A/C proteins as diverse signaling modulators might be biological key to unlocking the complex signaling of aging-related human diseases and homeostasis in cellular process.

摘要

随着核包膜蛋白核纤层蛋白在人类遗传疾病中的作用被发现,核纤层蛋白的更多不同作用也得到了阐明。核纤层蛋白的作用已在细胞稳态中得到探讨,包括基因调控、细胞周期、细胞衰老、脂肪生成、骨重塑以及对癌症生物学的调节。核纤层蛋白病的特征与氧化应激相关的细胞衰老、分化和寿命有关,并与衰老 - 氧化应激的下游过程有共同之处。因此,在本综述中,我们重点介绍了核纤层蛋白作为核维持关键分子的各种作用,特别是核纤层蛋白A/C,并且突变基因清楚地揭示了与衰老相关的遗传表型,如增强的分化、脂肪生成和骨质疏松症。核纤层蛋白A/C在干细胞分化、皮肤、心脏调节和肿瘤学中的调节作用也已得到阐明。除了核纤层蛋白病的最新进展外,我们首次强调了激酶依赖性核纤层蛋白生物学以及最近开发的核纤层蛋白调节机制或效应信号。将核纤层蛋白A/C蛋白作为多种信号调节剂的深入了解可能是解开衰老相关人类疾病复杂信号和细胞过程中稳态的生物学关键。

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