Similar Datasets
Project description:Knock down of Ifitm3 inhibits the adult retinal progenitor cell proliferation
| PRJNA736401 | ENA
Project description:Ifitm3 (interferon-inducible transmembrane protein 3) was previously identified as an endosomal antiviral effector protein that blocks viral infection1-4. In analyses of gene expression data from patients with B-cell leukemia and lymphoma, we identified Ifitm3 as one of the strongest predictors of poor clinical outcome. In normal resting B-cells, Ifitm3 was minimally expressed and mainly localized in endosomes. However, engagement of the B-cell receptor (BCR) and PI3K-activation strongly induced expression of Ifitm3 and phosphorylation of its N-terminus at Y20, resulting in accumulation at the cell surface. In B-cell leukemia, oncogenic kinases induced phosphorylation at Y20, resulting in constitutive plasma membrane localization of Ifitm3. Ifitm3¯ / ¯ naïve B-cells developed at normal numbers, however, B-cell activation upon antigen encounter, germinal center formation and production of antigen-specific antibodies were compromised. Likewise, oncogenes that typically induce development of leukemia and lymphoma failed to transform Ifitm3¯ / ¯ B-cells. Conversely, a phosphomimetic mutation of Y20 induced oncogenic PI3K-signaling and initiated transformation of premalignant B-cells into overt leukemia. Functional experiments revealed a previously unrecognized function of Ifitm3 as PIP3-scaffold and central amplifier of PI3K signaling downstream of the BCR and adhesion receptors. PI3K signal-amplification depends on binding of Ifitm3 to PIP3 via two lysine residues (K83 and K104) in its conserved intracellular loop. In Ifitm3¯ / ¯ B-cells, lipid rafts were depleted of PIP3, resulting in defective expression of >60 lipid raft-associated surface receptors, which impaired BCR-signaling and cellular adhesion. We conclude that phosphorylation of IFITM3 upon Bcell antigen-encounter induces a dynamic switch from antiviral effector functions in endosomes to a PI3K-amplification loop at the cell surface. IFITM3-dependent amplification of PI3K-signaling downstream of the BCR and adhesion receptors is critical to enable rapid expansion of B-cells with high affinity to antigen. In addition, multiple oncogenes depend on IFITM3 to assemble PIP3- dependent signaling complexes and amplify PI3K-signaling for malignant transformation.
2020-10-13 | GSE155305 | GEO
Project description:WT or IFITM3-KO mice were infected with PR8 H1N1 influenza virus and reinfected with X31 H3N2 influenza virus
2021-11-22 | GSE183890 | GEO
Project description:wild-type (WT) IFITM3 and 4KR-IFITM3 comparative interactome identified by Mass Spectrometry in THP1
2023-03-07 | PXD038896 | Pride
Project description:Targeting tumor-infiltrating Treg cells is an efficient way to evoke an anti-tumor immune response. How Treg cells fragility and stability are regulated remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. Conversely, the decreased IFITM3 protein and mRNA levels present in STAT1-deficient Treg cells indicate that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of TI-Tregs in the tumor model. Overall, our study demonstrates that the perturbation of TI-Tregs through IFNγ-IFITM3-STAT1 feedback is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.
2023-11-21 | GSE248223 | GEO
Project description:To study the effect of knocking down wingless-related MMTV integration site 2 (Wnt2) expression by RNAi on the growth and signaling pathways of ex vitro-cultured keloid fibroblasts (KFB).Human KFB were isolated from 10 keloid patient specimens. The KFB cells were then transfected with 4 pairs of small interfering RNA (siRNA) targeting human Wnt2, respectively. Reverse transcriptase-polymerase chain reaction and Western blot analysis were conducted to verify the knock down of Wnt2, and the expression of ?-catenin glycogen synthase kinase-3? (GSK-3?) and cyclin D1 were examined.siRNA Wnt2 transfection (siWnt2) resulted in the significant inhibition of Wnt2 expression at both the mRNA and protein levels. The expression of ?-catenin, GSK-3?, p-GSK-3?, and cyclin D1 at the protein level also decreased in siWnt2 cells. siWnt2 resulted in a substantially slower growth and significant delay in cell doubling time of the KFB cells compared with control groups. Further, the siRNA knock down of GSK-3? and ?-catenin resulted in slower proliferation rates, respectively.Wnt2 siRNA has an inhibitive effect on keloid fibroblast proliferation, which may be a potential therapeutic approach for keloid and other human fibrotic diseases.
| S-EPMC6156062 | biostudies-literature
Project description:In this study monoclonal cell lines carrying mutations in IFITM3 gene were obtained based on WI-38 VA13 cells. To research the involvement of the IFITM3 gene in cellular response to Influenza A virus infection, original WI-38 VA13 cells and the clones with depressed IFITM3 gene activity (F3, F5, Е12) were infected with influenza A/Puerto Rico/8/1934 (H1N1) virus. RNA-seq analysis of infected cell lines after 24 h was performed on an Illumina NextSeq 500 platform. The same mock-infected cells were used as controls (0 hpi). PolyA RNA-enriched fraction was used for constructing of cDNA libraries. Differential expressed genes were identified using R package DESeq2.
2023-12-16 | E-MTAB-13582 | biostudies-arrayexpress
Project description:Retinal microvascularization can provide important informations to systemic vascular phenomena. The non-invasive quantitative description of the retinal vascularization is now possible by performing OCT-angiography and their image analysis software (vascular density and retinal perfusion). Systemic microvacular changes during the establishment of oncological treatment by targeted antiangiogenic therapy are little described in the literature. The objective of this pilot study is to describe the evolution of the retinal vascular density of patients with antiangiogenic drugs. In addition, the evolution of the retinal vascular density of patients on antiangiogenic drugs will study as a function of the response to the treatment and the toxicity of these treatments.
| 2382594 | ecrin-mdr-crc
Project description:To investigate the role of IFITM3 in B-ALL, patient derived xenograft cells PDX2 were transduced with either a the constitutively membrane associated IFITM3-Y20E mutant or EV control. Additional mutation of PIP3 binding sites within the conserved internal loop region - K83/K104 or R85/R87/K88 - were introduced to test the predicted function of these sites.
2020-12-18 | PXD020696 | Pride
Project description:Given our laboratory interest in IFITM3 S-fatty-acylation and antiviral activity, we sought to directly characterize fatty acids that are covalently attached to the Cys residues of IFITM3. IFITM3 comprises two S-fatty-acylation sites (C71 and C72) in proximity of a intramembrane domain, and another site adjacent to a transmembrane domain (C105). We directly identified the S-fatty-acylation sites of IFITM3 and further demonstrated that the highly conserved Cys residues are primarily modified by palmitic acid.
2018-03-28 | PXD008400 | Pride