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We have previously reported Israa, immune-system-released activating agent, as a novel gene nested in intron 8 of the mouse Zmiz1 gene. We have also shown that Israa encodes for a novel FYN-binding protein and might be involved in the regulation of T-cell activation. In this report, we demonstrate that Israa gene product regulates the expression of a pool of genes involved in T-cell activation and signaling. Real time PCR and GFP knock-in expression analysis showed that Israa is transcribed and expressed in the spleen mainly by CD3CD8 cells as well as in the thymus by CD3 (DP and DN), CD4SP and CD8SP cells at different developmental stages. We also showed that Israa is downregulated in T-cells following activation of T-cell receptor. Using yeast two-hybrid analysis, we identified ELF1, a transcription factor involved in T-cell regulation, as an ISRAA-binding partner. Transcriptomic analysis of an EL4 cell line overexpressing ISRAA revealed differential expression of several genes involved in T-cell signaling, activation and development. Among these genes, Prkcb, Mib2, Fos, Ndfip2, Cxxc5, B2m, Gata3 and Cd247 were upregulated whereas Itk, Socs3, Tigit, Ifng, Il2ra and FoxJ1 were downregulated. Our findings support the existence in mouse of a novel FYN-related T-cell regulation pathway involving the product of an intron-nested gene.
This article was published in the following journal.
Name: Molecular immunology
Angiopoietin-like protein 6, which is encoded by ANGPTL6 gene (also known as angiopoietin growth factor, AGF), has been extensively characterized with regard to its proposed functions as angiogenesis ...
Epidemiological studies have shown sex differences in prevalence of non-allergic asthma. Recent reports demonstrated negative effects of androgen signaling on group 2 innate lymphoid cells (ILC2s), ex...
We previously showed that the first intron of genes exhibits several interesting characteristics not seen in other introns: (1) it is the longest intron on average in almost all eukaryotes, (2) it pre...
Tertiary lymphoid organs named also tertiary lymphoid structures (TLS) often occur at sites of autoimmune inflammation, organ transplantation and cancer. Although the mechanisms for their formation/fu...
Intron gigantism, where genes contain megabase-sized introns, is observed across species, yet little is known about its purpose or regulation. Here we identify a unique gene expression program utilize...
This is a Phase II/III randomized, controlled, multicenter, open-label study designed to assess the safety, efficacy, and impact on quality of life of PEG Intron and INTRON® A and the pop...
This is a randomized, double-blind, multicenter trial testing 2 doses of PEG-Intron, 1.0mcg/kg/week and 3.0mcg/kg/week in heavily treatment-experienced HIV-infected patients compared to pl...
The purpose of this study is to see if PEG-Intron is safe and tolerated when given to children, to see how much gets into the blood and how long it stays in the blood, and to see how well ...
This is an open-label, single-arm, multicenter Phase II safety and efficacy study of combination therapy with pembrolizumab and PEG-Intron (Peginterferon alpha-2b) in patients with advance...
This is an open label, randomized, comparative, multi-center study. Subjects will be screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the sele...
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
A widely-expressed protein of approximately 400 to 500 amino acids. Its N-terminal region (DENN domain) interacts with RAB GTP-BINDING PROTEINS and may regulate AUTOPHAGY, as well as PROTEIN TRANSPORT to ENDOSOMES. Expansion of the GGGGCC hexanucleotide repeat in the first intron of the C9orf72 gene is associated with FRONTOTEMPORAL DEMENTIA with AMYOTROPHIC LATERAL SCLEROSIS (FTDALS1).
Specialized organs adapted for the reception of stimuli by the NERVOUS SYSTEM.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...