Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha- and beta-globin locus control regions and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase). The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors. This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages. The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk). Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption. Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles. The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein. Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta-thalassaemic (Hbbd-th3/Hbbd-th3) mice. We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly.
 ...
PMID:Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2. 846 89

Phenotype of P815 mouse mast cells changes markedly during culture in the peritoneal cavity of syngenic BDF1 mice. The cells, cultured for 1 week in the peritoneal cavity of syngenic BDF1 mice, proliferate and express high levels of L-histidine decarboxylase (HDC) and mouse mast cell protease (MMCP)-6 mRNAs, indicating the ability of P815 cells to differentiate toward mature connective tissue mast cells. Peritoneal fluid aspirated from P815-inoculated BDF1 mouse and added to cultured P815 cells in vitro was also found to induce HDC mRNA expression, suggesting that at least some of the humoral factors in the peritoneal fluid induce HDC mRNA transcription. Among the erythroid transcription factors, P815 cells expressed GATA-2 but not GATA-1 mRNA before and after the intraperitoneal incubation. In contrast, the expression of NF-E2 subunit p45 disappeared, while expression of subunit mafK was markedly reduced after incubation. Cotransfection assays using HDC-luciferase reporter and p45 and/or mafK expression constructs showed that NF-E2 affects the transactivation of HDC gene. These results suggest that NF-E2 is also an important transcription factor in mast cell differentiation.
 ...
PMID:Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. 891 Apr 69

NF-E2 belongs to the basic-leucine zipper family of dimeric transcription factors. It consists of a widely expressed 18 kDa subunit, related to chicken Maf proteins, and a tissue-restricted 45 kDa subunit, which contains a cnc domain. It is found almost exclusively in hematopoietic progenitors, and cells of the erythroid/mega/mast cell trilineage. NF-E2 is involved in regulation of globin gene transcription, acting through locus control regions (LCRs) upstream of the alpha and beta globin gene clusters. In addition, it is essential for normal platelet production. Targeted disruption of the gene encoding the 45 kDa subunit leads to severe thrombocytopenia but little if any defect in erythropoiesis, indicating that other molecules can substitute for p45 in red cell maturation in developing mice. However, retroviral integration within the p45 gene has been shown to disrupt erythroid differentiation in erythroleukemia cells; this suggests that p45 could, conceivably, be a target for pharmacologic interventions in patients with excess red cell production due to polycythemia vera.
 ...
PMID:The NF-E2 transcription factor. 967 75

Cap 'n' collar-basic leucine zipper (CNC-bZIP) proteins are widely implicated in developmental processes throughout different species. Evidence is accumulating that some of them are also participating in induced gene expression in the adult. Here we show that the three CNC-bZIP members NF-E2, Nrf1 and Nrf2 are constitutively expressed in the murine mast cell line CPII and that they form transcription factor complexes with several AP1 binding proteins. Upon induction, complexes are observed at the 2 x NF-E2 consensus binding site and the extended kappa3/AP1(+) site of the TNFalpha promoter. The interaction of Nrf1 with c -jun, junD, fosB and ATF2 in mast cells is in contrast to the recently reported binding of Nrf1 alone at the kappa3/AP1(-) site in dendritic cells. We speculated that this may be the result of the expression of isoforms of Nrf1 in mast cells. Using a PCR cloning strategy, we have isolated six novel splice variants of this transcription factor. Some of them have deleted the translational stop codon, resulting in an Nrf1 protein with an altered leucine zipper region. Expression of this altered binding/interaction domain interferes with TNFalpha induction, indicating an interaction of this splice variant with the active AP1/NF-AT complex at this promoter.
 ...
PMID:Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF alpha promoter in stimulated mast cells. 982 75

The growth factor receptor Kit is involved in hematopoietic and nonhematopoietic development. Mice bearing Kit defects lack mast cells; however, strains bearing different Kit alleles exhibit diverse phenotypes. Herein, we investigated factors underlying differential sensitivity to IgG-mediated arthritis in 2 mast cell-deficient murine lines: KitWsh/Wsh, which develops robust arthritis, and KitW/Wv, which does not. Reciprocal bone marrow transplantation between KitW/Wv and KitWsh/Wsh mice revealed that arthritis resistance reflects a hematopoietic defect in addition to mast cell deficiency. In KitW/Wv mice, restoration of susceptibility to IgG-mediated arthritis was neutrophil independent but required IL-1 and the platelet/megakaryocyte markers NF-E2 and glycoprotein VI. In KitW/Wv mice, platelets were present in numbers similar to those in WT animals and functionally intact, and transfer of WT platelets did not restore arthritis susceptibility. These data implicated a platelet-independent role for the megakaryocyte, a Kit-dependent lineage that is selectively deficient in KitW/Wv mice. Megakaryocytes secreted IL-1 directly and as a component of circulating microparticles, which activated synovial fibroblasts in an IL-1-dependent manner. Transfer of WT but not IL-1-deficient megakaryocytes restored arthritis susceptibility to KitW/Wv mice. These findings identify functional redundancy among Kit-dependent hematopoietic lineages and establish an unanticipated capacity of megakaryocytes to mediate IL-1-driven systemic inflammatory disease.
 ...
PMID:Megakaryocytes compensate for Kit insufficiency in murine arthritis. 2837 55