| Autor: |
Kai Su Greene, Lukey, Michael J., Xueying Wang, Blank, Bryant, Druso, Joseph E., Lin, Miao-chong J., Stalnecker, Clint A., Zhang, Chengliang, Abril, Yashira Negrón, Erickson, Jon W., Wilson, Kristin F., Hening Lin, Weiss, Robert S., Cerione, Richard A. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 12/26/2019, Vol. 116 Issue 52, p26625-26632, 8p |
| Abstrakt: |
The mitochondrial enzyme glutaminase (GLS) is frequently upregulated during tumorigenesis and is being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, a mitochondrial NAD+-dependent lysine deacylase, plays a key role in stabilizing GLS. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating GLS and thereby protecting it from ubiquitin-mediated degradation. Moreover, we show that SIRT5 is up-regulated during cellular transformation and supports proliferation and tumorigenesis. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. These findings reveal a mechanism for increasing GLS expression in cancer cells and establish a role for SIRT5 in metabolic reprogramming and mammary tumorigenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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