Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis
| Title: | Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis |
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| Authors: | Cen Zhang, Juan Liu, Yuhan Zhao, Xuetian Yue, Yu Zhu, Xiaolong Wang, Hao Wu, Felix Blanco, Shaohua Li, Gyan Bhanot, Bruce G Haffty, Wenwei Hu, Zhaohui Feng |
| Source: | eLife, Vol 5 (2016) |
| Publisher Information: | eLife Sciences Publications Ltd, 2016. |
| Publication Year: | 2016 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | GLS2, p53, Rac1, metastasis, tumor suppression, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/10727; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.10727 |
| Access URL: | https://doaj.org/article/22c62ddb3b184de1ad1026ebb99b808a |
| Accession Number: | edsdoj.22c62ddb3b184de1ad1026ebb99b808a |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.10727 |
| Published in: | eLife |
| Language: | English |