G3BP2: Structure and function

Jin, Ge; Zhang, Zhen; Wan, Jingjing; Guo, Shirong; Liu, Xia; Zhang, Weidong

doi:10.1016/j.phrs.2022.106548

Cited by 17 publications

(9 citation statements)

References 120 publications

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“…3B and S1B). We found that only one protein, G3BP2, was bound simultaneously in all three cell lines 15 . We found that G3BP2 and G2BP1 share 70% homologous sequences (Figure S1C) 19 ; therefore, we tested their expression with Western blotting.…”

Section: Trf-27 Bound To G3bps and Acted Independent Of Stress Granulesmentioning

confidence: 78%

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tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance

Liu

Gong

et al. 2023

Preprint

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Breast cancer, one lethal malignant tumor, is positive for HER2 in about 20% of patients. The efficacy of current treatments is limited by primary and secondary resistance to trastuzumab. tRNA-derived fragments (tRFs) have shown crucial regulatory roles in various cancers. This study aimed to evaluate the role of tRF-27 in regulating the resistance of HER2-positive breast cancer against trastuzumab.tRF-27 was highly expressed in trastuzumab-resistant cells, and its expression level could predict the resistance to trastuzumab. High expression of tRF-27 promoted the growth and proliferation of trastuzumab-exposed cells.RNA-pulldown assay and mass spectrometry were performed to identify Ras GTPase-activating protein-binding proteins 1 and 2 (G3BPs) (two proteins targeted by tRF-27); RNA-immunoprecipitation (RIP) to confirm their bindings; co-immunoprecipitation (co-IP) and RNA-pulldown assay to determine the binding domains between G3BPs and tRF-27.tRF-27 bound to the nuclear transport factor 2 like domain(NTF2 domain) of G3BPs through a specific sequence. tRF-27 relied on G3BPs and NTF2 domain to increase trastuzumab tolerance. tRF-27 competed with lysosomal associated membrane protein 1(LAMP1) for NTF2 domain, thereby inhibiting lysosomal localization of G3BPs and tuberous sclerosis complex(TSC). Overexpression of tRF-27 inhibited phosphorylation of TSCs and promoted the activation of mechanistic target of rapamycin complex 1(MTORC1) to enhance cell proliferation and entice the resistance of HER2-positive breast cancer against trastuzumab.

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Section: Trf-27 Bound To G3bps and Acted Independent Of Stress Granulesmentioning

confidence: 78%

“…Ras GTPase-activating protein-binding proteins 1 and 2 (G3BPs) are a family of RNA-binding proteins that include G3BP1 and G3BP2 in mammals 15,16 . Researchers have summarized the function of G3BPs from three aspects: RNA stabilization, protein subcellular localization, and stress granules assembling.…”

Section: Introductionmentioning

confidence: 99%

tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance

Liu

Gong

et al. 2023

Preprint

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“…[ 29 ] In particular, accumulating evidence suggests that G3BP2 participates in the initiation and progression of various tumors. [ 30 ] However, the precise role of G3BP2 in HCC progression remains unclear. A co‐immunoprecipitation assay (co‐IP) was performed to confirm the interaction between MAP4K4 and G3BP2 with endogenous proteins in HCC cells or exogenous proteins in HEK392T cells transfected with HA‐MAP4K4 and Flag‐G3BP2.…”

Section: Resultsmentioning

confidence: 99%

Peptide Transporter 1‐Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis

Song,

Zhang,

Liu

et al. 2024

Advanced Science

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Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy‐saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide‐induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

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“…Circulating levels of MG53 appear to influence the proliferation and migration of NSCLC cells directly via G3BP2. Instead of performing classical ubiquitination-dependent degradation functions, the amino terminus of MG53 physically interacts with G3BP2 and enhances its nuclear translocation, which may be a key mechanism by which MG53 inhibits the G3BP2-mediated formation of lung cancer tumors and stress granules ( 20 , 50 ). Furthermore, an in vitro study showed that rhMG53 inhibited the formation of stress granules and potentiated the cytotoxic effect of cisplatin on human NSCLC cells ( 20 ).…”

Section: Beneficial Effects Of Mg53 On Cancer Therapymentioning

confidence: 99%

Is MG53 a potential therapeutic target for cancer?

Du,

Li,

2023

Front. Endocrinol.

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Cancer treatment still encounters challenges, such as side effects and drug resistance. The tripartite-motif (TRIM) protein family is widely involved in regulation of the occurrence, development, and drug resistance of tumors. MG53, a member of the TRIM protein family, shows strong potential in cancer therapy, primarily due to its E3 ubiquitin ligase properties. The classic membrane repair function and anti-inflammatory capacity of MG53 may also be beneficial for cancer prevention and treatment. However, MG53 appears to be a key regulatory factor in impaired glucose metabolism and a negative regulatory mechanism in muscle regeneration that may have a negative effect on cancer treatment. Developing MG53 mutants that balance the pros and cons may be the key to solving the problem. This article aims to summarize the role and mechanism of MG53 in the occurrence, progression, and invasion of cancer, focusing on the potential impact of the biological function of MG53 on cancer therapy.

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G3BP2: Structure and function

Cited by 17 publications

References 120 publications

tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance

tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance

Peptide Transporter 1‐Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis

Is MG53 a potential therapeutic target for cancer?

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