Details

Autor(en) / Beteiligte

• Greene, Kai Su
• Lukey, Michael J.
• Wang, Xueying
• Blank, Bryant
• Druso, Joseph E.
• Lin, Miao-chong J.
• Stalnecker, Clint A.
• Zhang, Chengliang
• Abril, Yashira Negrón
• Erickson, Jon W.
• Wilson, Kristin F.
• Lin, Hening
• Weiss, Robert S.
• Cerione, Richard A.

Titel

SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2019-12, Vol.116 (52), p.26625-26632

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The mitochondrial enzyme glutaminase (GLS) is frequently up-regulated 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.