A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability

被引:177
作者
Gallouzi, IE
Parker, F
Chebli, K
Maurier, F
Labourier, E
Barlat, I
Capony, JP
Tocque, B
Tazi, J
机构
[1] Univ Montpellier 2, Inst Genet Mol Montpellier, CNRS, UMR 5535, Montpellier 5, France
[2] Rhone Poulenc Rorer SA, Ctr Rech Vitry Alfortville, Gene Med Dept, F-94403 Vitry Sur Seine, France
[3] Ctr Rech Biochim Macromol, CNRS, LP 9008, INSERM,U249, F-34293 Montpellier 1, France
关键词
D O I
10.1128/MCB.18.7.3956
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src homology 3 [SH3] binding protein), was previously identified based on its ability to bind the SH3 domain of RasGAP. Here we show that G3BP colocalizes and physically interacts with RasGAP at the plasma membrane of serum stimulated but not quiescent Chinese hamster lung fibroblasts, In quiescent cells, G3BP was hyperphosphorylated on serine residues, and this modification was essential for its activity. Indeed, G3BP harbors a phosphorylation-dependent RNase activity which specifically cleaves the 3'-untranslated region of human c-myc mRNA, The endoribonuclease activity of G3BP can initiate mRNA degradation and therefore represents a link between a RasGAP-mediated signaling pathway and RNA turnover.
引用
收藏
页码:3956 / 3965
页数:10
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