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线粒体融合蛋白 1/ TusC2 和细胞内钙离子稳态：肿瘤抑制、抗炎和抗衰老的意义。

Mitochondrial Fus1/Tusc2 and cellular Ca2 homeostasis: tumor suppressor, anti-inflammatory and anti-aging implications.

机构信息

Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Meharry Medical College, Nashville, TN, USA.

Vanderbilt Memory and Alzheimer's Center, Vanderbilt University, Nashville, TN, USA.

出版信息

Cancer Gene Ther. 2022 Oct;29(10):1307-1320. doi: 10.1038/s41417-022-00434-9. Epub 2022 Feb 18.

DOI:10.1038/s41417-022-00434-9
PMID:35181743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9576590/
Abstract

FUS1/TUSC2 (FUSion1/TUmor Suppressor Candidate 2) is a tumor suppressor gene (TSG) originally described as a member of the TSG cluster from human 3p21.3 chromosomal region frequently deleted in lung cancer. Its role as a TSG in lung, breast, bone, and other cancers was demonstrated by several groups, but molecular mechanisms of its activities are starting to unveil lately. They suggest that Fus1-dependent mechanisms are relevant in etiologies of diseases beyond cancer, such as chronic inflammation, bacterial and viral infections, premature aging, and geriatric diseases. Here, we revisit the discovery of FUS1 gene in the context of tumor initiation and progression, and review 20 years of research into FUS1 functions and its molecular, structural, and biological aspects that have led to its use in clinical trials and gene therapy. We present a data-driven view on how interactions of Fus1 with the mitochondrial Ca (mitoCa) transport machinery maintain cellular Ca homeostasis and control cell apoptosis and senescence. This Fus1-mediated cellular homeostasis is at the crux of tumor suppressor, anti-inflammatory and anti-aging activities.

摘要

FUS1/TUSC2（融合 1/肿瘤抑制候选物 2）是一种肿瘤抑制基因（TSG），最初被描述为人类 3p21.3 染色体区域 TSG 簇的成员，该区域在肺癌中经常缺失。多个研究小组证明了其在肺癌、乳腺癌、骨癌和其他癌症中的 TSG 作用，但最近才开始揭示其活性的分子机制。它们表明，Fus1 依赖性机制与癌症以外的疾病的病因有关，如慢性炎症、细菌和病毒感染、过早衰老和老年疾病。在这里，我们重新审视了 FUS1 基因在肿瘤起始和进展中的发现，并回顾了 20 年来对 FUS1 功能及其分子、结构和生物学方面的研究，这些研究导致了其在临床试验和基因治疗中的应用。我们提出了一种数据驱动的观点，即 Fus1 与线粒体 Ca（mitoCa）转运机制的相互作用如何维持细胞 Ca 稳态并控制细胞凋亡和衰老。这种 Fus1 介导的细胞稳态是肿瘤抑制、抗炎和抗衰老活性的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/66bfa47f5a34/41417_2022_434_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/0628fc6cbc82/41417_2022_434_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/66bfa47f5a34/41417_2022_434_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/0628fc6cbc82/41417_2022_434_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/ae769afc5498/41417_2022_434_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/e39c18b887d4/41417_2022_434_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/02c7a6a780d9/41417_2022_434_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a3/9576590/66bfa47f5a34/41417_2022_434_Fig5_HTML.jpg

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