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李斯特菌E3泛素连接酶与核糖体相关质量控制(RQC)机制。

LISTERIN E3 Ubiquitin Ligase and Ribosome-Associated Quality Control (RQC) Mechanism.

作者信息

Mishra Ribhav, Bansal Anurag, Mishra Amit

机构信息

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Karwar, Rajasthan, 342037, India.

Center for Converging Technologies, Jaipur, University of Rajasthan, Jaipur, 302001, India.

出版信息

Mol Neurobiol. 2021 Dec;58(12):6593-6609. doi: 10.1007/s12035-021-02564-x. Epub 2021 Sep 29.

Abstract

According to cellular demands, ribosomes synthesize and maintain the desired pool of proteins inside the cell. However, sometimes due to defects in ribosomal machinery and faulty mRNAs, these nascent polypeptides are constantly under threat to become non-functional. In such conditions, cells acquire the help of ribosome-associated quality control mechanisms (RQC) to eliminate such aberrant nascent proteins. The primary regulator of RQC is RING domain containing LISTERIN E3 ubiquitin ligase, which is associated with ribosomes and alleviates non-stop proteins-associated stress in cells. Mouse RING finger protein E3 ubiquitin ligase LISTERIN is crucial for embryonic development, and a loss in its function causes neurodegeneration. LISTERIN is overexpressed in the mouse brain and spinal cord regions, and its perturbed functions generate neurological and motor deficits, but the mechanism of the same is unclear. Overall, LISTERIN is crucial for brain health and brain development. The present article systematically describes the detailed nature, molecular functions, and cellular physiological characterization of LISTERIN E3 ubiquitin ligase. Improve comprehension of LISTERIN's neurological roles may uncover pathways linked with neurodegeneration, which in turn might elucidate a promising novel therapeutic intervention against human neurodegenerative diseases.

摘要

核糖体根据细胞需求在细胞内合成并维持所需的蛋白质库。然而,有时由于核糖体机制缺陷和错误的信使核糖核酸(mRNA),这些新生多肽一直面临着失去功能的威胁。在这种情况下,细胞借助核糖体相关质量控制机制(RQC)来清除此类异常的新生蛋白质。RQC的主要调节因子是含RING结构域的李斯特菌E3泛素连接酶,它与核糖体相关,可减轻细胞中与不停蛋白质相关的应激。小鼠RING指蛋白E3泛素连接酶李斯特菌对胚胎发育至关重要,其功能丧失会导致神经退行性变。李斯特菌在小鼠脑和脊髓区域过度表达,其功能紊乱会导致神经和运动缺陷,但其机制尚不清楚。总体而言,李斯特菌对大脑健康和大脑发育至关重要。本文系统地描述了李斯特菌E3泛素连接酶的详细性质、分子功能和细胞生理学特征。更好地理解李斯特菌的神经学作用可能会揭示与神经退行性变相关的途径,进而可能阐明一种针对人类神经退行性疾病的有前景的新型治疗干预措施。

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