The N-terminal domain of G3BP enhances cell motility and invasion by posttranscriptional regulation of BART.
Mol Cancer Res, 2011/7;9(7):856-66.
Taniuchi K[1], Nishimori I, Hollingsworth MA
Affiliations
PMID: 21665939DOI: 10.1158/1541-7786.MCR-10-0574
Impact factor: 6.333
Abstract
The regulation of mRNA stability plays an important role in the control of gene expression during cell motility and invasion. We previously reported that GTPase-activating protein [Src homology 3 (SH3) domain] binding protein (G3BP), a marker of cytoplasmic stress granules that are formed in stressed cells and regulate mRNA stability, binds and degrades the mRNA of binder of Arl two (BART) that inhibits retroperitoneal invasion and hepatic metastasis of pancreatic cancer cells. Here, we report that overexpression of the amino (N)-terminal region of G3BP, including the binding region for BART mRNA, dominant-negatively inhibits formation of the complex between endogenous G3BP and BART mRNA, and increases the expression of BART. This, in turn, inhibits the invasiveness of pancreatic cancer cells. On the other hand, the carboxy (C)-terminal region of G3BP is associated with phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) that initiates stress granule assembly but does not modulate the posttranscriptional regulation of BART mRNA. N-terminal G3BP also plays a role in regulating secreted matrix metalloproteinases, transcription factors, and a variety of genes involved in cell adhesion and motility. These results suggest that N-terminal G3BP contributes to posttranscriptional regulation of cell motility and invasive capacity of pancreatic cancer.
MeSH terms
Carcinoma, Pancreatic Ductal; Carrier Proteins; Cell Line, Tumor; Cell Movement; DNA Helicases; Eukaryotic Initiation Factor-2; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Oxidative Stress; Pancreatic Neoplasms; Phosphorylation; Poly-ADP-Ribose Binding Proteins; Protein Structure, Tertiary; RNA Helicases; RNA Processing, Post-Transcriptional; RNA Recognition Motif Proteins; RNA Stability; Transcription Factors
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