Crystal structure of IFIT2 (ISG54) predicts functional properties of IFITs

Sen, Ganes C.; Fensterl, Volker

doi:10.1038/cr.2012.130

Cited by 28 publications

(26 citation statements)

References 15 publications

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“…Therefore, IFNs exert important effects on tumor suppression by participating in immunosurveillance and immunoediting [15]. Different types of IFNs bind to distinct cell surface receptors, trigger the JAK/STAT signaling pathway and transcriptionally induce the expressions of ISGs [16, 17]. IFIT2, also known as ISG54, is one important member of ISGs, and numerous studies have shown that it plays an important role in anti-viral and anti-cancer effects [9].…”

Section: Discussionmentioning

confidence: 99%

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Chen

Zhai

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: The status of interferon (IFN) signaling pathway has been shown to be closely associated with the response of immune checkpoint blockade therapy against advanced human cancers. IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), also known as IFN-stimulated gene 54 (ISG54), is one of the most highly responsive ISGs, which can inhibit the proliferation and migration of cancer cells, and regulate viral replication, resulting in anti-cancer and anti-viral effects. In the present study, we aimed to investigate the role of IFIT2 in human gastric cancer. Methods: Immunohistochemistry assay was used to investigate the correlation between the IFIT2 expression in cancer tissues and clinical parameters of gastric cancer patients. Knockdown of IFIT2 was performed using RNAi to assess the role of IFIT2 in the regulation of biological behaviors in human gastric cancer cell lines. Results: IFIT2 expression in gastric cancer tissues was significantly associated with tumor stage and postoperative prognoses of the patients. Moreover, decreased IFIT2 expression in human gastric cancer cell lines SGC-7901 and AGS significantly increased the cell viability, cell migration and the ratios of cells in S phase. Conclusion: Our present study demonstrated that the decreased IFIT2 expression could promote the gastric cancer progression and predict poor therapeutic outcomes of the patients.

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Section: Discussionmentioning

confidence: 99%

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Chen

Zhai

Zheng

et al. 2017

Cell Physiol Biochem

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“…[13][14][15][16] IFIT2 regulates the functions of cell cycle, apoptosis, tumor colonization and viral replication, which confer cellular resistance to viral infections and regulates proliferation, apoptosis and migration of cancer cells. [17][18][19][20] In this report, we found that curcumin induced expression of interferon regulatory genes (especially IFIT2) in luekemia cell U937. upregulation of IFIT2 by exogenous expressing or treating with IFNg in K562 increased cells apoptosis and enhanced anticancer effect of curcumin.…”

Section: Introductionmentioning

confidence: 83%

Curcumin induces apoptosis in human leukemic cell lines through an IFIT2-dependent pathway

Zhang

Kong

Liu

et al. 2017

Cancer Biology & Therapy

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Curcumin, the primary bioactive component isolated from turmeric, has been shown to possess variety of biologic functions including anti-cancer activity. However, molecular mechanisms in different cancer cells are various. In the present study, we demonstrated that curcumin induced G2/M cell cycle arrest and apoptosis by increasing the expression levels of cleaved caspase-3, cleaved PARP and decreasing the expression of BCL ¡ 2 in U937 human leukemic cells but not in K562 cells. We found some interferon induced genes, especially interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), were significantly upregulated when treated with curcumin in U937 cells by gene expression chip array, and further confirmed that the expression of IFIT2 was obviously higher in U937 than that in K562 cells by Western blot assay. In addition, inhibiting the expression of IFIT2 by shRNA in U937 rescued curcumininduced apoptosis and exogenous overexpression of IFIT2 by lentiviral transduction or treating with IFNg in K562 cells enhanced anti-cancer activity of curcumin. These results indicated for the first time that curcumin induced leukemic cell apoptosis via an IFIT2-dependent signaling pathways. The present study identified a novel mechanism underlying the antitumor effects of curcumin, and may provide a theoretical basis for curcumin combined with interferon in the cancer therapeutics.

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“…Previous studies suggested that targeting both the proteasome-dependent pathways and the aggresome pathway in tumor cells with bortezomib could induce marked accumulation of polyubiquitinated proteins and significant cell stress, promoting, in turn, the activation of autophagy and apoptosis 27, 28. IFIT2, an IFN-induced protein containing nine TPR domains, forms complexes by interacting with virus RNAs, other ISG proteins, or other binding partners to execute various functions including antiviral, antitumor, and as a regulator of transcription and translation 6. The formation of aggresome of IFIT2 resulted in cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The IFIT2 gene codes for a protein with nine tetratricopeptide repeats (TPR) motifs, which has also been designated as IFIT2 5, 6. TPR, a 34-amino acid motif folding into a helix-turn-helix, is most often present in cassettes of multiple repeats and mediates protein-protein interactions 7, 8.…”

Section: Introductionmentioning

confidence: 99%

“…IFIT2 was reported to interact with different proteins and RNA. IFIT2 regulates the functions of cell cycle, apoptosis, tumor colonization, and viral replication, which confer cellular resistance to viral infections and regulates proliferation, apoptosis, and migration of cancer cells 6, 12-14. Moreover, IFIT2 has been demonstrated to be a cytoskeleton-associated protein.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Proteasome Activity Induces Aggregation of IFIT2 in the Centrosome and Enhances IFIT2-Induced Cell Apoptosis

Chen¹,

Liu²,

Xu³

et al. 2017

Int. J. Biol. Sci.

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IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), one of the most highly responsive interferon-stimulated genes, inhibits the proliferation and migration of cancer cells and regulates viral replication. IFIT2 has been demonstrated to be a cytoskeleton-associated protein that becomes enriched in the mitotic spindle of cells. However, the molecular mechanisms by which IFIT2 executes biological functions are largely unclear. The findings of this study showed that inhibiting the activation of proteasome led to the enrichment of IFIT2 and induced the aggregation of IFIT2 protein in the centrosome. Microtubule inhibitor colchicine and dynein inhibitor ciliobrevin inhibited the proteasome inhibitor-induced aggregation of IFIT2 protein in the centrosome. Intriguingly, IFIT2 and proteasome inhibitor worked together to induce the apoptosis of cancer cells. The results of the present study revealed that the inhibition of proteasome activity blocked the degradation of IFIT2 and promoted the aggregation of IFIT2 in the centrosome, which in turn induced cell apoptosis. In short, IFIT2 may be a potential target for cancer therapeutics.

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Crystal structure of IFIT2 (ISG54) predicts functional properties of IFITs

Cited by 28 publications

References 15 publications

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Curcumin induces apoptosis in human leukemic cell lines through an IFIT2-dependent pathway

Inhibition of Proteasome Activity Induces Aggregation of IFIT2 in the Centrosome and Enhances IFIT2-Induced Cell Apoptosis

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