Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis

Cen Zhang, Juan Liu, Yuhan Zhao, Xuetian Yue, Yu Zhu, Xiaolong Wang, Hao Wu, Felix Blanco, Shaohua Li, Gyan Bhanot, Bruce Haffty, Wenwei Hu, Zhaohui Feng

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Glutaminase (GLS) isoenzymes GLS1 and GLS2 are key enzymes for glutamine metabolism. Interestingly, GLS1 and GLS2 display contrasting functions in tumorigenesis with elusive mechanism; GLS1 promotes tumorigenesis, whereas GLS2 exhibits a tumor-suppressive function. In this study, we found that GLS2 but not GLS1 binds to small GTPase Rac1 and inhibits its interaction with Rac1 activators guanine-nucleotide exchange factors, which in turn inhibits Rac1 to suppress cancer metastasis. This function of GLS2 is independent of GLS2 glutaminase activity. Furthermore, decreased GLS2 expression is associated with enhanced metastasis in human cancer. As a p53 target, GLS2 mediates p53’s function in metastasis suppression through inhibiting Rac1. In summary, our results reveal that GLS2 is a novel negative regulator of Rac1, and uncover a novel function and mechanism whereby GLS2 suppresses metastasis. Our results also elucidate a novel mechanism that contributes to the contrasting functions of GLS1 and GLS2 in tumorigenesis.

Original languageEnglish (US)
Article numbere10727
JournaleLife
Volume5
Issue numberJANUARY2016
DOIs
StatePublished - Jan 28 2016

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Glutaminase
Monomeric GTP-Binding Proteins
Neoplasm Metastasis
Carcinogenesis
Guanine Nucleotide Exchange Factors
Neoplasms
Glutamine
Isoenzymes
Metabolism
Tumors
Enzymes
Display devices

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Zhang, Cen ; Liu, Juan ; Zhao, Yuhan ; Yue, Xuetian ; Zhu, Yu ; Wang, Xiaolong ; Wu, Hao ; Blanco, Felix ; Li, Shaohua ; Bhanot, Gyan ; Haffty, Bruce ; Hu, Wenwei ; Feng, Zhaohui. / Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis. In: eLife. 2016 ; Vol. 5, No. JANUARY2016.
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Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis. / Zhang, Cen; Liu, Juan; Zhao, Yuhan; Yue, Xuetian; Zhu, Yu; Wang, Xiaolong; Wu, Hao; Blanco, Felix; Li, Shaohua; Bhanot, Gyan; Haffty, Bruce; Hu, Wenwei; Feng, Zhaohui.

In: eLife, Vol. 5, No. JANUARY2016, e10727, 28.01.2016.

Research output: Contribution to journalArticle

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AU - Wang, Xiaolong

AU - Wu, Hao

AU - Blanco, Felix

AU - Li, Shaohua

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AU - Haffty, Bruce

AU - Hu, Wenwei

AU - Feng, Zhaohui

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