The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis

Gómez-Herranz, Maria; Nekulova, Marta; Faktor, Jakub; Hernychová, Lenka; Kote, Sachin; Sinclair, Elizabeth H.; Nenutil, Rudolf; Vojtěšek, Bořivoj; Ball, Kathryn L.; Hupp, Ted R.

doi:10.1016/j.cellsig.2019.03.024

Cited by 28 publications

(58 citation statements)

References 74 publications

(108 reference statements)

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“…To filter out target peptide spectrum matches over the decoy-peptide spectrum matches, a fixed FDR of 1% was set at the peptide level. Mass recalibration and label-free quantification (LFQ) of area under the curve MS1 peaks were carried out using Proteome Discoverer nodes, Spectrum Files RC, Minora Feature Detector, and Feature Mapper ( 31 , 32 , 33 , 34 , 35 , 36 , 37 ). Minora Feature Detector is the dominant algorithm behind the LFQ whereby it first detects chromatographic peaks in the raw spectral data and maps them to identified peptide spectrum matches.…”

Section: Methodsmentioning

confidence: 99%

Proteomic Dissection of the Impact of Environmental Exposures on Mouse Seminal Vesicle Function

Skerrett‐Byrne

Trigg

Bromfield

et al. 2021

Molecular & Cellular Proteomics

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Seminal vesicles are an integral part of the male reproductive accessory gland system. They produce a complex array of secretions containing bioactive constituents that support gamete function and promote reproductive success, with emerging evidence suggesting these secretions are influenced by our environment. Despite their significance, the biology of seminal vesicles remains poorly defined. Here, we complete the first proteomic assessment of mouse seminal vesicles and assess the impact of the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or control daily for five consecutive days prior to collecting seminal vesicle tissue. A total of 5013 proteins were identified in the seminal vesicle proteome with bioinformatic analyses identifying cell proliferation, protein synthesis, cellular death, and survival pathways as prominent biological processes. Secreted proteins were among the most abundant, and several proteins are linked with seminal vesicle phenotypes. Analysis of the effect of acrylamide on the seminal vesicle proteome revealed 311 differentially regulated (FC ± 1.5, p ≤ 0.05, 205 up-regulated, 106 downregulated) proteins, orthogonally validated via immunoblotting and immunohistochemistry. Pathways that initiate protein synthesis to promote cellular survival were prominent among the dysregulated pathways, and rapamycin-insensitive companion of mTOR (RICTOR, p = 6.69E-07) was a top-ranked upstream driver. Oxidative stress was implicated as contributing to protein changes, with acrylamide causing an increase in 8-OHdG in seminal vesicle epithelial cells (fivefold increase, p = 0.016) and the surrounding smooth muscle layer (twofold increase, p = 0.043). Additionally, acrylamide treatment caused a reduction in seminal vesicle secretion weight (36% reduction, p = 0.009) and total protein content (25% reduction, p = 0.017). Together these findings support the interpretation that toxicant exposure influences male accessory gland physiology and highlights the need to consider the response of all male reproductive tract tissues when interpreting the impact of environmental stressors on male reproductive function.

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Section: Methodsmentioning

confidence: 99%

Proteomic Dissection of the Impact of Environmental Exposures on Mouse Seminal Vesicle Function

Skerrett‐Byrne

Trigg

Bromfield

et al. 2021

Molecular & Cellular Proteomics

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“…A previous study reported that both IRF1 and IFI6 are positively associated with the drug-specific chemosensitivity of gastric cancer ( 56 ). Gómez-Herranz et al ( 57 ) revealed that IRF1 is one of the most dominant IFN-γ inducible proteins whose synthesis is attenuated in IFITM1/IFITM3-negative cervical cancer cells. Yang et al ( 58 ) reported that IRF1 could directly bind to one site of the IFI35 promoter and mediate IFN-γ-dependent transcriptional activation of IFI35 in HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

IRF1 regulates the progression of colorectal cancer via interferon‑induced proteins

et al. 2021

Int J Mol Med

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Radiation is one of the main methods for the treatment of colorectal cancer (CRC) before or after surgery. However, radiotherapy tolerance of patients with CRC is often a major concern. Interferon regulatory factor 1 (IRF1) is a member of the IRF family and is involved in the development of multiple diseases, including tumors. The present study investigated the role of IRF1 in the development and radiation sensitivity of CRC. Immunohistochemistry was performed to examine the expression levels of IRF1 in tissue samples from patients with CRC, as well as in nude mice. MTT, 5-ethynyl-20-deoxyuridine, colony formation, cell cycle alteration and apoptosis assays were performed in CRC cell lines. Western blotting and immunofluorescence were used to detect the expression levels of a series of proteins. RNA sequencing was applied to identify genes whose expression was upregulated by IRF1 overexpression. Xenograft nude mouse models and hematoxylin and eosin staining were used to validate the present findings in vivo . It was revealed that the expression levels of IRF1 were significantly lower in CRC tissues than in adjacent tissues. IRF1 upregulation inhibited cell proliferation and colony formation, caused G 1 cell arrest, promoted cell apoptosis, and enhanced the sensitivity of CRC cells to X-ray irradiation. The role of IRF1 in promoting the radiosensitivity of CRC was further demonstrated in nude mice with CRC xenografts. In addition, RNA sequencing revealed that overexpression of IRF1 in CRC cells significantly increased the expression levels of interferon-induced protein family members interferon α inducible protein 6, interferon induced transmembrane protein 1 and interferon induced protein 35 (fold change >2.0). In summary, the present study demonstrated that the upregulation of IRF1 inhibited the progression and promoted the radiosensitivity of CRC, likely by regulating interferon-induced proteins.

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“…It has been reported that IFITMs are involved in various cellular processes, which has both direct and indirect effects on immunity ( 58 ). A recent study showed that the expression levels of IRF1, human leucocyte antigen (HLA)-B, and ISG15 protein were attenuated in the IFITM1/IFITM3 double-null cells ( 59 ). Consistently, the ectopic expression of EcIFITM1 significantly increased the levels of IRF7, ISG15, and MXI mRNA, while knockdown of EcIFITM1 displayed an opposite effect.…”

Section: Discussionmentioning

confidence: 99%

Grouper Interferon-Induced Transmembrane Protein 1 Inhibits Iridovirus and Nodavirus Replication by Regulating Virus Entry and Host Lipid Metabolism

Wang

Zheng

et al. 2021

Front. Immunol.

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Interferon-induced transmembrane proteins (IFITMs) are novel viral restriction factors which inhibit numerous virus infections by impeding viral entry into target cells. To investigate the roles of IFITMs during fish virus infection, we cloned and characterized an IFITM1 homolog from orange spotted grouper (Epinephelus coioides) (EcIFITM1) in this study. EcIFITM1 encodes a 131-amino-acid polypeptide, which shares 64 and 43% identity with Seriola dumerili and Homo sapiens, respectively. The multiple sequence alignment showed that EcIFITM1 contained five domains, including NTD (aa 1–45), IMD (aa 46–67), CIL (aa 68–93), TMD (aa 94–119), and CTD (aa 120–131). In vitro, the level of EcIFITM1 mRNA expression was significantly up-regulated in response to Singapore grouper iridovirus (SGIV), or red-spotted grouper nervous necrosis virus (RGNNV) infection. EcIFITM1 encoded a cytoplasmic protein, which was partly colocalized with early endosomes, late endosomes, and lysosomes. The ectopic expression of EcIFITM1 significantly inhibited the replication of SGIV or RGNNV, which was demonstrated by the reduced virus production, as well as the levels of viral gene transcription and protein expression. In contrast, knockdown of EcIFITM1 using small interfering RNAs (siRNAs) promoted the replication of both viruses. Notably, EcIFITM1 exerted its antiviral activity in the step of viral entry into the host cells. Furthermore, the results of non-targeted lipometabolomics showed that EcIFITM1 overexpression induced lipid metabolism remodeling in vitro. All of the detected ceramides were significantly increased following EcIFITM1 overexpression, suggesting that EcIFITM1 may suppress SGIV entry by regulating the level of ceramide in the lysosomal system. In addition, EcIFITM1 overexpression positively regulated both interferon-related molecules and ceramide synthesis-related genes. Taken together, our results demonstrated that EcIFITM1 exerted a bi-functional role, including immune regulation and lipid metabolism in response to fish virus infections.

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The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis

Cited by 28 publications

References 74 publications

Proteomic Dissection of the Impact of Environmental Exposures on Mouse Seminal Vesicle Function

Proteomic Dissection of the Impact of Environmental Exposures on Mouse Seminal Vesicle Function

IRF1 regulates the progression of colorectal cancer via interferon‑induced proteins

Grouper Interferon-Induced Transmembrane Protein 1 Inhibits Iridovirus and Nodavirus Replication by Regulating Virus Entry and Host Lipid Metabolism

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