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MORC 蛋白家族相关特征与人类疾病和癌症。

MORC protein family-related signature within human disease and cancer.

机构信息

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, 110122, China.

Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.

出版信息

Cell Death Dis. 2021 Nov 27;12(12):1112. doi: 10.1038/s41419-021-04393-1.

Abstract

The microrchidia (MORC) family of proteins is a highly conserved nuclear protein superfamily, whose members contain common domain structures (GHKL-ATPase, CW-type zinc finger and coiled-coil domain) yet exhibit diverse biological functions. Despite the advancing research in previous decades, much of which focuses on their role as epigenetic regulators and in chromatin remodeling, relatively little is known about the role of MORCs in tumorigenesis and pathogenesis. MORCs were first identified as epigenetic regulators and chromatin remodelers in germ cell development. Currently, MORCs are regarded as disease genes that are involved in various human disorders and oncogenes in cancer progression and are expected to be the important biomarkers for diagnosis and treatment. A new paradigm of expanded MORC family function has raised questions regarding the regulation of MORCs and their biological role at the subcellular level. Here, we systematically review the progress of researching MORC members with respect to their domain architectures, diverse biological functions, and distribution characteristics and discuss the emerging roles of the aberrant expression or mutation of MORC family members in human disorders and cancer development. Furthermore, the illustration of related mechanisms of the MORC family has made MORCs promising targets for developing diagnostic tools and therapeutic treatments for human diseases, including cancers.

摘要

微体(MORC)家族蛋白是一个高度保守的核蛋白超家族,其成员含有共同的结构域(GHKL-ATPase、CW 型锌指和卷曲螺旋结构域),但表现出多种生物学功能。尽管在过去几十年中进行了大量的研究,其中大部分集中在它们作为表观遗传调节剂和染色质重塑的作用上,但对于 MORC 在肿瘤发生和发病机制中的作用知之甚少。MORC 最初被鉴定为生殖细胞发育中的表观遗传调节剂和染色质重塑因子。目前,MORC 被认为是涉及多种人类疾病的疾病基因和癌症进展中的癌基因,有望成为诊断和治疗的重要生物标志物。MORC 家族功能扩展的新范例提出了关于 MORC 调节及其在亚细胞水平上的生物学功能的问题。在这里,我们系统地回顾了 MORC 成员在其结构域结构、多种生物学功能和分布特征方面的研究进展,并讨论了 MORC 家族成员异常表达或突变在人类疾病和癌症发展中的新兴作用。此外,MORC 家族相关机制的阐明使 MORC 成为开发人类疾病(包括癌症)诊断工具和治疗方法的有前途的靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea9/8627505/afaa2f806f2e/41419_2021_4393_Fig1_HTML.jpg

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