G3BP1

Official Full Name

G3BP stress granule assembly factor 1

Organism

Homo sapiens

Gene ID

10146

Background

This gene encodes one of the DNA-unwinding enzymes which prefers partially unwound 3'-tailed substrates and can also unwind partial RNA/DNA and RNA/RNA duplexes in an ATP-dependent fashion. This enzyme is a member of the heterogeneous nuclear RNA-binding proteins and is also an element of the Ras signal transduction pathway. It binds specifically to the Ras-GTPase-activating protein by associating with its SH3 domain. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

Synonyms

G3BP; HDH-VIII

Cat.No.	Product Name	Price
CSC-DC005997	Panoply™ Human G3BP1 Knockdown Stable Cell Line	Inquiry
CSC-SC005997	Panoply™ Human G3BP1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD06501Z	Human G3BP1 adenoviral particles	Inquiry
LV13239L	human G3BP1 (NM_005754) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH298209	shRNA set against Mouse G3BP1 (NM_013716.2)	Inquiry
SHH072479	shRNA set against Human G3BP1(NM_005754.2)	Inquiry
SHH298205	shRNA set against Human G3BP1 (NM_005754.2)	Inquiry
SHH298213	shRNA set against Rat G3BP1 (NM_133565.1)	Inquiry
SHW000244	shRNA set against Chicken G3BP1 (NM_001006150)	Inquiry
SHW016208	shRNA set against Danio rerio G3BP1 (NM_199956)	Inquiry

Cat.No.	Product Name	Price
CDCL110057	Mouse G3bp1 ORF clone (NM_013716.2)	Inquiry
CDFG012588	Human G3BP1 cDNA Clone(NM_198395.1)	Inquiry
CDFH007240	Human G3BP1 cDNA Clone(NM_005754.2)	Inquiry
CDFH007241	Human G3BP1 cDNA Clone(NM_005754.2)	Inquiry
MiUTR1H-03893	G3BP1 miRNA 3'UTR clone	Inquiry
MiUTR1M-10222	G3BP1 miRNA 3'UTR clone	Inquiry
MiUTR3H-09997	G3BP1 miRNA 3'UTR clone	Inquiry
CDCB161719	Chicken G3BP1 ORF Clone (NM_001006150)	Inquiry
CDCB177683	Danio rerio G3BP1 ORF Clone (NM_199956)	Inquiry
CDCB189035	Rabbit G3BP1 ORF clone (XM_008255288.1)	Inquiry
CDCG004738	Rat G3BP1 ORF clone(NM_133565.1)	Inquiry
CDCR291243	Human G3BP1 ORF Clone(NM_005754.2)	Inquiry
CDCR325843	Human G3BP1 ORF Clone(NM_198395.1)	Inquiry
CDCS412408	Human G3BP1 ORF Clone (BC006997)	Inquiry

Detailed Information

The RasGAP SH3 domain binding proteins (G3BPs) are a highly conserved family of multi-functional RNA binding proteins. Recently, accumulating evidence has indicated that G3BPs play predominant roles in controlling critical cellular processes that include growth, proliferation and apoptosis. The G3BP family includes two members in mammals, ie, G3BP1 and G3BP2. G3BP1 knockout mice exhibit growth retardation, embryonic lethality and increased apoptotic cell death. Conversely, the overexpression of G3BP1 has been shown to induce S-phase entry with elevated cell proliferation. The G3BP1 protein is upregulated in a diversity of tumors and may present a novel target for cancer therapy. So far, the mechanisms by which G3BP1 executes its functions remain obscure, but prior studies have implicated G3BP1 in the modulation of RNA metabolism, Ras signaling, and the ubiquitin proteasome pathway.

G3BP1 and innate immune antiviral responses

Stress granules (SGs) are cytoplasmic storage sites containing translationally silenced mRNAs which can be released to resume translation after stress subsides. G3BP1 is extremely important for SG assembly. Depletion of G3BP1 inhibits SG formation in response to several stressors, and overexpression of G3BP1 nucleates SG formation independent of additional stressors. It reported that large G3BP1-induced SGs, but not small granules, are capable of triggering eIF2α phosphorylation through PKR, resulting in translational repression. Together with data indicating G3BP1 is targeted by many viruses, these properties suggested that G3BP1 is an antiviral protein important in innate immunity. The studies show that G3BP1 is an antiviral protein that activates the transcriptional arm of the innate immune response by NFκB and JNK transcription, and release of certain cytokines. G3BP1 is also involved in recruitment and activation of PKR at SGs, indicating G3BP1 regulates protein synthesis through PKR as part of a broad innate immune response. Strikingly, close proximity of G3BP1 and PKR within cells coincides with PKR activation, and the G3BP1 PxxP domain is required for PKR activation and antiviral activity of G3BP1. These data indicate that G3BP1 mediates crosstalk between stress responses and innate immunity and is an antiviral protein itself.

G3BP1 and Cancer

G3BP1 is known to contain an RNA recognition motif (RRM) by which exerts its mRNA-stabilizing or mRNA-degrading effects. The dysregulation of G3BP1 interactions with its target mRNAs may result in cancer development and progression. Some cancer-related gene, such as CTNNB1, c-MYC, and PMP22, have been implicated in the regulation of G3BP1 in this way. In human sarcomas, lung cancer, gastric cancer, colon cancer and breast cancer, G3BP1 has been found to be highly expressed. High expression of G3BP1 can promote the proliferation and motility of gastric cancer or breast cancer cells. Downregulation of G3BP1 in sarcoma xenografts prevented tumor invasion and completely blocked lung metastasis in mouse models. By binding with p53, G3BP1 led to the redistribution of p53 from the nucleus to the cytoplasm and affected cell apoptosis. These reports suggest the vital roles of G3BP1 in tumorigenesis.

Recently, researchers investigated the expression and functional role of G3BP1 in hepatocellular carcinoma (HCC). They found that G3BP1 was frequently upregulated in HCC samples and upregulated G3BP1 expression was correlated with poor survival. Further cell biological results indicated that G3BP1 promoted HCC cell migration and Slug protein was identified as one of the main effectors of G3BP1. Therefore, the study provides new insights into the role of G3BP1 in tumor and suggests that G3BP1 may be a potential target for HCC treatment.

References:

Martin S, et al. Deficiency of G3BP1, the stress granules assembly factor, results in abnormal synaptic plasticity and calcium homeostasis in neurons. Journal of Neurochemistry, 2013, 125(2):175–184.
Mao C, et al. A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53. Cancer Research, 2018, 78(13):3484.
Tsai W C, et al. Arginine demethylation of G3BP1 promotes stress granule assembly. Journal of Biological Chemistry, 2016, 291(43):jbc.M116.739573.
Dou N, et al. G3BP1 contributes to tumor metastasis via upregulation of Slug expression in hepatocellular carcinoma. American Journal of Cancer Research, 2016, 6(11):2641.
Aulas A, et al. G3BP1 promotes stress-induced RNA granule interactions to preserve polyadenylated mRNA. Journal of Cell Biology, 2015, 209(1):73.
Winslow S, et al. Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells. Molecular Cancer, 2013, 12(1):156.
Reineke L C, Lloyd R E. The Stress Granule Protein G3BP1 Recruits Protein Kinase R To Promote Multiple Innate Immune Antiviral Responses. Journal of Virology, 2015, 89(5):2575.

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