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 Ca2+ (mitoCa2+) transport machinery maintain cellular Ca2+ 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.

Details

Title
Mitochondrial Fus1/Tusc2 and cellular Ca2+ homeostasis: tumor suppressor, anti-inflammatory and anti-aging implications
Author
Uzhachenko, Roman 1 ; Shimamoto, Akiko 2 ; Chirwa, Sanika S. 1 ; Ivanov, Sergey V. 3 ; Ivanova, Alla V. 4   VIAFID ORCID Logo  ; Shanker, Anil 5   VIAFID ORCID Logo 

1  Meharry Medical College, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Nashville, USA (GRID:grid.259870.1) (ISNI:0000 0001 0286 752X) 
2  Meharry Medical College, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Nashville, USA (GRID:grid.259870.1) (ISNI:0000 0001 0286 752X); Vanderbilt University, Vanderbilt Memory and Alzheimer’s Center, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
3  Vanderbilt University, Department of Cell and Developmental Biology, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
4  Meharry Medical College, School of Graduate Studies and Research, Nashville, USA (GRID:grid.259870.1) (ISNI:0000 0001 0286 752X) 
5  Meharry Medical College, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Nashville, USA (GRID:grid.259870.1) (ISNI:0000 0001 0286 752X); Vanderbilt University, Host-Tumor Interactions Research Program, Vanderbilt-Ingram Cancer Center, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217); Vanderbilt University, Vanderbilt Institute for Infection, Immunology and Inflammation, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217); Vanderbilt University, Vanderbilt Memory and Alzheimer’s Center, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
Pages
1307-1320
Publication year
2022
Publication date
Oct 2022
Publisher
Nature Publishing Group
ISSN
09291903
e-ISSN
14765500
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41417-022-00434-9
ProQuest document ID
2725463442
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.