Send to

Choose Destination
Elife. 2016 Jan 11;5:e10727. doi: 10.7554/eLife.10727.

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

Author information

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, United States.
Department of Neurosurgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Surgery, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, United States.
Department of Molecular Biology, Biochemistry & Physics, Rutgers, The State University of New Jersey, Piscataway, United States.


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.


GLS2; Rac1; chromosomes; genes; human; metastasis; mouse; p53; tumor suppression

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center