Topic
Ifi202
About: Ifi202 is a research topic. Over the lifetime, 32 publications have been published within this topic receiving 2146 citations.
Papers
TL;DR: The data indicate that type-I IFNs are important mediators in the pathogenesis of murine lupus, and that reducing their activity in the human counterpart may be beneficial.
Abstract: Indirect evidence suggests that type-I interferons (IFN-α/β) play a significant role in the pathogenesis of lupus. To directly examine the contribution of these pleiotropic molecules, we created congenic NZB mice lacking the α-chain of IFN-α/βR, the common receptor for the multiple IFN-α/β species. Compared with littermate controls, homozygous IFN-α/βR-deleted NZB mice had significantly reduced anti-erythrocyte autoantibodies, erythroblastosis, hemolytic anemia, anti-DNA autoantibodies, kidney disease, and mortality. These reductions were intermediate in the heterozygous-deleted mice. The disease-ameliorating effects were accompanied by reductions in splenomegaly and in several immune cell subsets, including B-1 cells, the major producers of anti-erythrocyte autoantibodies. Decreases of B and T cell proliferation in vitro and in vivo, and of dendritic cell maturation and T cell stimulatory activity in vitro were also detected. Absence of signaling through the IFN-α/βR, however, did not affect increased basal levels of the IFN-responsive p202 phosphoprotein, encoded by a polymorphic variant of the Ifi202 gene associated with the Nba2 predisposing locus in NZB mice. The data indicate that type-I IFNs are important mediators in the pathogenesis of murine lupus, and that reducing their activity in the human counterpart may be beneficial.
573 citations
TL;DR: It is suggested that increased expression of Ifi202 gene (encoding p202 protein) in immune cells contributes to lupus susceptibility, and increased levels of IFI16 protein in human SLE patients are associated with the diseases.
131 citations
TL;DR: It is reported here that p202 binds the cell growth regulatory retinoblastoma protein (pRb) in vitro and in vivo, and is the first interferon-inducible protein found to bind pRb.
119 citations
TL;DR: A human IFN-γ-inducible gene, IFI 16, is reported, which has nucleotide sequence similarity with portions of two of the mouse genes, Ifi202 and Ifi204, which is present as a single copy gene in the human genome.
Abstract: A cluster of at lest six interferon-γ (IFNγ)-inducible genes designated Ifi201-204 and located on mouse chromosome 1 has recently been described. Here , we report a human IFN-γ-inducible gene, IFI 16, which has nucleotide sequence similarity with portions of two of the mouse genes, Ifi202 and Ifi204. A full-length cDNA clone derived from IFI 16 [2.709 kilobases (kb)] contained a single open reading frame of 2.187 kb which encoded a putative polypeptide of 729 amino acids and a predicted non-glycosylated M
r
of 80020. IFI 16 mRNA was found to be constitutively expressed in lymphoid cells and in cell lines of both the T and B lineages. By contrast, the mRNA was not expresed by the cell lines HL-60, U937, and K562, which represent early stages of myeloid development, but was strongly inducible in HL-60 and U937 with IFN-γ. The IFI 16 protein demonstrated a putative domain structure with patchy similarity to the proteins expressed from gene Ifi202 and Ifi204. The mouse and human proteins each contain two analogous ≈200 amino acid domains which are imperfect copies, but IFI 16 demonstrated additional unique regions, including a Lys-rich N-terminal portion and a “spacer” region between the reiterated domains, analogous to spacer regions in the CD5 and CD8α molecules. Using a panel of inter-species somatic cell hybrid cell lines, IFI 16 was localized to the chromosomal region 1q12→1qter, a region systenic between mouse an man. DNA blotting indicated that, in contrast to the mouse, IFI 16 is present as a single copy gene in the human genome. The authors are pleased to make the cDNA clones described in this paper available to interested investigators.
95 citations
TL;DR: Using the antiserum, it is established that the 202 protein is a 52-kD phosphoprotein whose level in cells from various murine lines can be increased up to 16-fold upon treatment with IFN-alpha.
Abstract: Recently, we reported that an interferon (IFN)-inducible, murine 72-kD phosphoprotein (the 204 protein) that is encoded by the Ifi 204 gene from the gene 200 cluster is localized in the nucleolus and the nucleoplasm. We have now raised a polyclonal antiserum against the 202 protein that is encoded by the Ifi 202 gene from the same gene cluster and regions of which are homologous to those from the 204 protein. Using the antiserum, we established that the 202 protein is a 52-kD phosphoprotein whose level in cells from various murine lines can be increased up to 16-fold upon treatment with IFN-alpha. Experiments involving fractionation of cell lysates and indirect immunofluorescence microscopy of cultured cells revealed that the 202 protein was localized in the cytoplasm and the nucleus. Upon treatment of cells with IFN, the 202 protein first accumulated on the surface of a cytoplasmic, membranous fraction and after prolonged treatment with IFN it was localized mainly in the nucleus. In IFN-treated mitotic AKR cells, the 202 protein was colocalized with chromosomes. 202 protein extracted from IFN-treated AKR cells bound double-stranded DNA in vitro. Studies on 202 protein function should be facilitated by the availability of complete cDNA clones and the finding of cell lines and an inbred strain of mice in which the expression of this protein was impaired.
82 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2014 | 1 |
| 2012 | 2 |
| 2011 | 3 |
| 2010 | 4 |
| 2009 | 2 |
| 2008 | 3 |