The Type I Interferon Receptor: Structure, Function, and Evolution of a Family Business

Mogensen, K. E.; Lewerenz, Malte; Reboul, Jérôme; Lutfalla, Georges; Uzé, Gilles

doi:10.1089/107999099313019

Cited by 229 publications

(164 citation statements)

References 214 publications

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“…Moreover, PRMT1 appeared to regulate IFN signalling by association with IFN receptor [20]. In fish, a recent study failed to identify IFNAR-1 homologue in the putative IFN receptor gene cluster of pufferfish [44].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Caiwen

Zhang

Lü

et al. 2007

Fish & Shellfish Immunology

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Section: Discussionmentioning

confidence: 99%

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Caiwen

Zhang

Lü

et al. 2007

Fish & Shellfish Immunology

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“…Interferonα (IFN)-α, which belongs to the type I IFN, is a multifunctional cytokine exerting immunomodulatory, antiviral, and anticancer effects [4][5][6] . It interacts with the IFN-α/β receptor on the cell surface to induce the activation of JAK/STAT1 (Janus activated kinase/signal transducers and activators of transcription 1) pathway to regulate the transcription of the genes controlling antiproliferative activities [6] .…”

Section: Introductionmentioning

confidence: 99%

Interferon-α enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis

Yuan

Zhu

Huang³

et al. 2007

Acta Pharmacol Sin

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Aim: To determine whether interferon-α (IFNα) can enhance doxorubicin sensitivity in osteosarcoma cells and its molecular mechanism. Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was studied using Flow cytometry analysis, Hoechst33258 staining, DNA fragmentation assay, as well as the activation of caspase-3 and poly (ADP-ribose) polymerase. Protein expression was detected by Western blotting. The dependence of p53 was determined using p53-siRNA transfection. Results: IFNα increased doxorubicin-induced cytotoxicity to a much greater degree through apoptosis in human osteosarcoma p53-wild U2OS cells, but not p53-mutant MG63 cells. IFNα markedly upregulated p53, Bax, Mdm2, and p21, downregulated Bcl-2, and activated caspase-3 and PARP cleavage in response to doxorubicin in U2OS cells. Moreover, the siRNA-mediated silencing of p53 significantly reduced the IFNα/doxorubicin combination-induced cytotoxicity and PARP cleavage. Conclusion: IFNα enhances the sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis. The proper combination with IFNα and conventional chemotherapeutic agents may be a rational strategy for improving the treatment of osteosarcoma with functional p53.

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“…Type I interferons (IFN␣, -␤, and -) 1 possess a wide variety of actions among which the antiviral and antiproliferative activities have captured most of the attention because of their potential therapeutic uses (21)(22)(23). Binding of type I IFNs to their receptors results in the activation of kinases of the Jak family (Jak1 and Tyk2), which are responsible for tyrosine phosphorylation of latent cytoplasmic transcription factors designated as signal transducers and activators of transcription 1 and 2 (STAT1 and STAT2).…”

mentioning

confidence: 99%

Different Requirements for the Cytostatic and Apoptotic Effects of Type I Interferons

Sandoval¹,

Xue²,

Pilkinton³

et al. 2004

Journal of Biological Chemistry

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The regulation of cell growth is one of the most important effects of type I interferons (IFNs). This response may involve a cytostatic effect or the induction of apoptosis depending on the cell context. Often the growthinhibitory response of type I IFNs is studied in tumor cell lines carrying mutations of tumor suppressor genes, and therefore, the growth-inhibitory effect can be influenced by inactivation of these important regulators of cell proliferation. In this report, we explored the role of the ARF-p53 pathway in the growth-inhibitory effect of type I IFNs. We found that p53 is only induced in cells that express p14 ARF (p19 ARF in mouse cells). Surprisingly, mouse embryonal fibroblasts that are null for p19 ARF or P53, even after transformation with oncogenic RAS, respond as well as wild type to the growth-inhibitory effect of type I IFNs. Similarly, human ARF ؊/؊ U2OS and P53 ؊/؊ SAOS-2 cells show a significant decrease in cell proliferation. However, only SAOS-2 or U2OS reconstituted with inducible p14 ARF undergo apoptosis in response to IFN␤ treatment, and this effect was not inhibited by expression of dominant negative p53. These data suggest that (i) at least in specific cell types, the induction of apoptosis by type I IFNs requires an ARF pathway that is p53-independent and (ii) the cytostatic and pro-apoptotic effects of type I IFNs employ different pathways.The product of the retinoblastoma gene, RB (for recent reviews see Refs. 1-4), regulates the passage from G 1 to S phase by tightly controlling the restriction point (reviewed in Refs. 1-6). Malignant transformation always involves deregulation of the restriction point by either the absence of functional RB, the amplification of cyclin D or CDK4, or the loss of p16 INK4a (1, 4). However, additional events are required for the emergence of a malignant phenotype, because hyperproliferative signals trigger built-in safety mechanisms that result in cell cycle arrest/senescence or apoptosis. The main effector of this safety mechanism is the ARF-MDM2-p53 pathway. For instance, the absence of RB triggers not only the transcription of S phase genes but also p19 ARF , which in turn inhibits MDM2, allowing p53 to stop cell cycle progression and induce apoptosis or senescence (7-9). The ARF-MDM2-p53 pathway is also a safety net for the activation of oncogenes such as RAS, MYC, v-Abl, and E1A. These mechanisms explain why most tumors not only have alterations of the RB pathway (i.e. either inactivation of tumor suppressors RB or INK4A, or amplification of cyclin D or CDK4/6) but also mutations in P53 or ARF that allow cells to escape cell cycle arrest and/or apoptosis. Thus, it is not surprising to find in many cancers the INK4A locus, which encodes both p16 and p19 ARF deleted and inactivated by methylation and/or mutated (10 -20).Type I interferons (IFN␣, -␤, and -) 1 possess a wide variety of actions among which the antiviral and antiproliferative activities have captured most of the attention because of their potential therapeutic uses (21-23). Bindi...

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The Type I Interferon Receptor: Structure, Function, and Evolution of a Family Business

Cited by 229 publications

References 214 publications

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

Interferon-α enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis

Different Requirements for the Cytostatic and Apoptotic Effects of Type I Interferons

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