Disease relevance of G3BP1

• These findings demonstrate for the first time the receptor-dependent regulation of G3BP, a downstream effector of Ras signaling, by HRG, a growth factor with diverse functions in breast cancer cells [1].
• METHODS: Synovial tissues from patients with RA or osteoarthritis (OA), as well as from healthy controls, were analyzed for galectins 1 and 3 and G3BP by in situ hybridization and immunohistochemistry [2].
• CONCLUSION: Our results indicate that G3BP was implicated in cancer metastasis because of its differential expressions in the two panels of cell sublines with different metastatic potentials [3].
• Vaccinia virus intermediate stage transcription is complemented by Ras-GTPase-activating protein SH3 domain-binding protein (G3BP) and cytoplasmic activation/proliferation-associated protein (p137) individually or as a heterodimer [4].

High impact information on G3BP1

• The RasGAP-associated endoribonuclease G3BP assembles stress granules [5].
• In antigen-specific T cells, endogenous G3BP moved into a intracellular location adjacent to the immune synapse, but deeper inside the cell, upon antigen recognition [6].
• Conversely, elimination of endogenous G3BP by RNA interference increased Lck Y505 phosphorylation and reduced TCR signaling [6].
• As a consequence, G3BP augmented T-cell activation as measured by interleukin-2 gene activation [6].
• A number of the genes assigned to the CDR represent good candidates for the 5q- syndrome, including MEGF1, G3BP, and several of the novel gene predictions [7].

Chemical compound and disease context of G3BP1

• G3BP was also overexpressed in human breast tumors in parallel with HER2 overexpression and in an estrogen-independent manner, suggesting a role for G3BP in cancer progression [1].

Biological context of G3BP1

• Up-regulation of G3BP was found in MCF7 breast cancer cells overexpressing HER2 [1].
• The endoribonuclease activity of G3BP can initiate mRNA degradation and therefore represents a link between a RasGAP-mediated signaling pathway and RNA turnover [8].
• This suggests that G3BP is a nuclear transport factor, as hypothesized previously, and that viral infection may alter RNA transport [9].
• The G3BP (ras-GTPase-Activating Protein SH3-Domain-Binding Protein) family of proteins has been implicated in both signal transduction and RNA-metabolism [10].
• In the present study, we determined the dynamics of the association among G3BP1, IMP1, and HuD with polysomes through P19 neuronal differentiation as well as the functional effect of these proteins on tau mRNA translation [11].

Anatomical context of G3BP1

• Quantitative reverse transcriptase-polymerase chain reaction showed that the expressed levels of G3BP mRNA in fragile X lymphoblast cell lines were significantly less than controls [12].
• 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 [8].
• CONCLUSION: Our data indicate that galectin 3 and G3BP are not only involved in inflammation, but also contribute to the activation of synovial fibroblasts [2].
• RESULTS: In RA, galectin 3 messenger RNA and protein stained throughout the synovial membrane, whereas G3BP was particularly expressed at sites of bone destruction [2].
• Levels of galectin 3 and G3BP in serum and synovial fluid from patients with RA and OA and controls, as well as in cell culture supernatants, were determined by enzyme-linked immunosorbent assay (ELISA) [2].

Associations of G3BP1 with chemical compounds

• Here, we show that G3BP, a phosphorylation-dependent endoribonuclease that interacts with RasGAP, is recruited to SGs in cells exposed to arsenite [5].
• In quiescent cells, G3BP was hyperphosphorylated on serine residues, and this modification was essential for its activity [8].
• Exogenous supplementation of glutathione inhibited SG formation elicited by arsenate or G3BP [13].
• It should be emphasized that these results do not necessarily indicate a direct interaction of integrin with G3BP1 and rasGap120 [14].

Physical interactions of G3BP1

• The USP10/G3BP complex appears to co-immunoprecipitate with ubiquitinated species that could be substrates of USP10 [15].
• Upregulation of the RAS-GTPase activating protein (GAP)-binding protein (G3BP) in proliferating RPE cells [16].

Regulatory relationships of G3BP1

• Our results indicate that G3BP mRNA may be regulated by FMRP and supports the hypothesis that FMRP may modulate the transcription of specific transcripts [12].
• Furthermore, recombinant G3BP and p137 expressed individually or together in mammalian or bacterial cells complemented the activity of the viral RNA polymerase and transcription factors [4].
• We also show that G3BP promotes S phase entry in cultured fibroblasts deprived of serum and that this function is dependent on the presence of the RNA binding domain of the protein [17].

Other interactions of G3BP1

• This interaction was further confirmed by performing a 2HS with G3BP, which led to the isolation of USP10 encoding cDNAs [15].
• Microsequencing of the polypeptide showed that this enzyme corresponds to G3BP, an element of the Ras pathway which binds specifically to the GTPase-activating protein [18].
• HDH VIII/G3BP is analogous to the heterogeneous nuclear ribonucleoproteins and contains a sequence rich in RGG boxes similar to the C-terminal domain of HDH IV/nucleolin, another DNA and RNA helicase [18].
• Indeed, G3BP harbors a phosphorylation-dependent RNase activity which specifically cleaves the 3'-untranslated region of human c-myc mRNA [8].
• In addition, we show a strong, negative effect on translation of the tau mRNA by IMP1, G3BP1, and HuD proteins in HEK-293 cells [11].

Analytical, diagnostic and therapeutic context of G3BP1

• In vitro, RA synovial fibroblasts showed an increased release of galectin 3 into culture medium, as measured by ELISA, but decreased secretion of G3BP [2].
• Sequence alignment displayed its identity with the 3'-end of the coding sequence of the human RAS-GTPase activating protein (GAP)-binding protein (G3BP) [16].
• Immunoelectron microscopy showed that a portion of Sindbis nsP3 is localized at the nuclear envelope, suggesting a possible site of G3BP recruitment to nsP3-containing complexes [9].
• Northern blot analysis and immunoblotting experiments showed enhanced expression of G3BP in all tumor samples as compared to healthy tissue [17].
• Collectively, these results suggest that G3BP1 and rasGap120 can be recruited to sites of integrin ligation where they may play a role in cytoskeletal reorganization [14].

References