Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00554282" target="_blank" >RIV/61388963:_____/22:00554282 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1038/s42255-021-00524-2" target="_blank" >https://doi.org/10.1038/s42255-021-00524-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s42255-021-00524-2" target="_blank" >10.1038/s42255-021-00524-2</a>

Result language
angličtina
Original language name
Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth
Original language description
Tumors can reprogram the functions of metabolic enzymes to fuel malignant growth, however, beyond their conventional functions, key metabolic enzymes have not been found to directly govern cell mitosis. Here, we report that glutamine synthetase (GS) promotes cell proliferation by licensing mitotic progression independently of its metabolic function. GS depletion, but not impairment of its enzymatic activity, results in mitotic arrest and multinucleation across multiple lung and liver cancer cell lines, patient-derived organoids and xenografted tumors. Mechanistically, GS directly interacts with the nuclear pore protein NUP88 to prevent its binding to CDC20. Such interaction licenses activation of the CDC20-mediated anaphase-promoting complex or cyclosome to ensure proper metaphase-to-anaphase transition. In addition, GS is overexpressed in human non-small cell lung cancer and its depletion reduces tumor growth in mice and increases the efficacy of microtubule-targeted chemotherapy. Our findings highlight a moonlighting function of GS in governing mitosis and illustrate how an essential metabolic enzyme promotes cell proliferation and tumor development, beyond its main metabolic function.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GJ18-24473Y" target="_blank" >GJ18-24473Y: Strategies to identify the vulnerabilities of cancer cells</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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