| RRC ID |
77020
|
| 著者 |
Zhang C, Liu J, Zhao Y, Yue X, Zhu Y, Wang X, Wu H, Blanco F, Li S, Bhanot G, Haffty BG, Hu W, Feng Z.
|
| タイトル |
Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis.
|
| ジャーナル |
Elife
|
| 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.
|
| 巻・号 |
5
|
| ページ |
e10727
|
| 公開日 |
2016-1-11
|
| DOI |
10.7554/eLife.10727
|
| PII |
e10727
|
| PMID |
26751560
|
| PMC |
PMC4749555
|
| MeSH |
Cell Line, Tumor
Glutaminase / metabolism*
Humans
Neoplasm Metastasis*
Protein Binding
Tumor Suppressor Protein p53 / metabolism*
rac1 GTP-Binding Protein / metabolism*
|
| IF |
7.08
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
