Vis Cancer Med
Volume 4, 2023
|Number of page(s)||3|
|Published online||17 January 2023|
Commentaries And Historical Reflections
Licensing instead of fueling: Glutamine synthetase promotes mitotic progression via a non-metabolic mechanism
Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310000, PR China
2 Cancer Center, Zhejiang University, Hangzhou 310000, PR China
* Corresponding authors: email@example.com (Z. Lu), firstname.lastname@example.org (Y.-X. Feng)
Accepted: 21 December 2022
A recent report published in Nature Metabolism identified that glutamine synthetase (GS), the only enzyme in mammals to produce glutamine from glutamate, can directly control cancer cell mitosis by governing the APC/C complex via a metabolism-independent mechanism. It reported that GS can directly interact with the nuclear pore protein NUP88 to abolish its binging with CDC20, therefore licensing the activation of APC/CCDC20 to permit proper metaphase to anaphase transition of mitosis. These findings illustrated a dual-function mode of action of GS in cancer cells, in which GS’s metabolic and non-metabolic functions coordinate with the concentration change of glutamine in the tumor microenvironment (TME) to ensure cell survival or proliferation, respectively. These findings revealed the multi-faceted roles of glutamine synthetase in tumor development and underscored the potential to target non-canonical functions of glutamine synthetase for cancer treatment.
Key words: Glutamine synthetase / Mitosis / APC/C
© The Authors, published by EDP Sciences, 2023
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