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 SCL gene encodes a putative transcription factor with a basic helix-loop-helix (B-HLH) motif and is known to be predominantly expressed in erythroid cells. Here we also demonstrate expression of SCL mRNA in normal mast cells, mast cell lines and megakaryocytic cell lines. SCL is therefore expressed in the same three lineages as GATA-1, a well-recognized hemopoietic transcription factor. SCL and GATA-1 mRNA were also co-expressed in interleukin 3-dependent primitive myeloid lines. In murine erythroleukemia (MEL) cells SCL and GATA-1 underwent coordinated biphasic modulation during hexamethylene bisacetamide (HMBA)-induced erythroid differentiation. The kinetics of SCL and GATA-1 mRNA expression was inversely correlated with changes in ID, a negative regulator of B-HLH proteins, and was distinct from changes in MYC, MYB and erythropoietin receptor transcripts. During myeloid differentiation of K562 cells, SCL and GATA-1 mRNA levels also underwent biphasic modulation. Thus SCL and GATA-1 are coordinately expressed in multiple hemopoietic lineages and coordinately regulated during induced erythroid and myeloid differentiation. In nonhemopoietic tissues SCL was only detected in adult and developing brain where GATA-1 is reportedly not expressed. In day 14.5 embryos analysed by in situ hybridization, SCL transcripts were detected in post-mitotic neurons in the metencephalon and roof of the mesencephalon. This suggests a previously unexpected role for SCL in neural differentiation.
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PMID:SCL is coexpressed with GATA-1 in hemopoietic cells but is also expressed in developing brain. 156 64

The basic helix-loop-helix (bHLH) transcription factors form heterodimers and control steps in cellular differentiation. We have studied four bHLH transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage-defined progenitors and hematopoietic growth factor-dependent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-defined progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted pattern of expression, although expression was seen in some bi- and unilineage progenitors. No expression was detected in erythroid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcription factor, was also widely expressed in all bi- and unilineage progenitors; only the trilineage erythroid-megakaryocyte-macrophage progenitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors showing expression and some not. This was seen even when two sister cells from the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1, E12, and lyl-1 showed marked variation at different points in cell cycle in isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and that their expression in hematopoietic cells varies in response to cytokines and/or during transit through cell cycle.
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PMID:Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors. 876 52

We have used various mouse mutants for studying the development of mast cells. The bone marrow origin of mast cells was shown by using giant granules of beige mice as a marker. Mast cell-deficient W/W(v) and Sl/Sl(d) mice are useful for investigation of the developmental processes. The mi locus encodes a member of the basic helix-loop-helix-leucine zipper protein family of transcription factors (MITF), and mast cells of mi/mi mice showed phenotypic abnormalities. Mast cells of mi/mi mice synthesized the mutant mi-MITF in normal amounts, and mi-MITF showed an inhibitory effect on the transcription of various mast cell-specific genes. On the other hand, mice of tg/tg possess the transgene insertional mutation in the 5' flanking region of the mi gene and do not express any MITFs. Genes whose transcription was suppressed were more numerous in mast cells of mi/mi mice than in those of tg/tg mice. The comparison between phenotypes of mi/mi mast cells and those of tg/tg mast cells gave some insights into the regulation of mast cell phenotypes by transcription factors.
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PMID:Mutant mice: a useful tool for studying the development of mast cells. 1130 15

Mutation of microphthalmia transcription factor (MITF) results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. The primary cell types affected in MITF-deficient mice are melanocytes, osteoclasts and mast cells. A search for MITF-associated proteins, using a mast cell library that was screened with a construct that encodes the basic helix-loop-helix leucine zipper (bHLH-Zip) domain of MITF, resulted in the isolation of the protein kinase C interacting (PKCI) protein 1 and protein inhibitor of activated STAT3 (PIAS3). We have accumulated clear evidence of a function for these two proteins as repressors of MITF-induced transcriptional activity. Here, we describe this evidence and ideas that give some insight into the cellular network of interactions between various transcription factors and MITF.
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PMID:The function of MITF and associated proteins in mast cells. 1221 80

MITF is a basic helix-loop-helix leucine zipper-type transcription factor and is important for development of mast cells. MITF encoded by Mi(wh) allele (Mi(wh)-MITF) was mutated at a single amino acid of basic domain, and possessed a deficient but apparent DNA-binding ability. Here, we characterized the unique effects of Mi(wh)-MITF on the expression of mast cell-related genes. The expression level of mouse mast cell protease (mMCP)-4, -5, and -6 genes in Mi(wh)/Mi(wh) cultured mast cells (CMCs) was intermediate between levels of normal (+/+) CMCs and tg/tg CMCs, which did not express any MITFs. Mi(wh)-MITF appeared to show the positive transactivation effect through the remaining DNA-binding ability. On the other hand, the expression level of tryptophan hydroxylase gene was lower in Mi(wh)/Mi(wh) CMCs than in tg/tg CMCs, suggesting the inhibitory effect of Mi(wh)-MITF on the transactivation. Mi(wh)-MITF possessed dual abnormal effects on transactivation of mast cell-related genes.
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PMID:Dual abnormal effects of mutant MITF encoded by Mi(wh) allele on mouse mast cells: decreased but recognizable transactivation and inhibition of transactivation. 1222 May 16

Mutation of microphthalmia transcription factor (MITF) results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. A search for MITF-associated proteins, using a mast cell library that was screened with a construct that encodes the basic helix-loop-helix leucine zipper (Zip) domain of MITF, resulted in the isolation of the STAT3 inhibitor, PIAS3. PIAS3 functions in vivo as a key molecule in suppressing the transcriptional activity of MITF. Here, we report that the Zip domain is the region of MITF that is involved in the direct interaction between MITF and PIAS3. Additionally, we investigated the effect of phosphorylation of MITF on its interaction with PIAS3. We found that phosphorylation of MITF on serines in positions 73 and 409 plays an important role in its association with PIAS3. This effect was profound with phosphorylation on Ser409, which significantly reduced the inhibitory effect of PIAS3 on MITF and also modulated the transcriptional activity of MITF. Thus, phosphorylation of MITF could be considered a fine, and alternative, tuning of its transcriptional machinery.
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PMID:Role played by microphthalmia transcription factor phosphorylation and its Zip domain in its transcriptional inhibition by PIAS3. 1464 19

Mast cells are progeny of multipotential hematopoietic stem cells (MHSCs). MHSCs commit to the mast cell lineage in the bone marrow, and the mast cell-committed progenitors leave the bone marrow, migrate in blood, invade connective or mucosal tissue, and then proliferate and differentiate to connective tissue-type or mucosal mast cell. GATA-1, GATA-2, and PU.1 transcription factors seem to be involved i the commitment to mast cells, and MITF, a basic helix-loop-helix leucine zipper-type transcription factor, seems to be involved in the migration, phenotypic expression, and survival of mast cells. KIT ligand (KITL) is the most important cytoline for development of mast cells, and KIT is the receptor of KITL. Tissues of loss-of-function mutants of KIT, KITL, or MITF are deficient in mast cells.
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PMID:Molecular mechanisms of mast cell development. 1693 Dec 85

The Microphthalmia-associated transcription factor (Mitf) is an essential basic helix-loop-helix leucine zipper transcription factor for mast cell development. Mice deficient in Mitf harbor a severe mast cell deficiency, and Mitf-mutant mast cells cultured ex vivo display a number of functional defects. Therefore, an understanding of the genetic program regulated by Mitf may provide important insights into mast cell differentiation. Multiple, distinct isoforms of Mitf have been identified in a variety of cell types; we found that Mitf-a, Mitf-e, and Mitf-mc were the major isoforms expressed in mast cells. To determine the physiologic function of Mitf in mast cells, we restored expression of these isoforms in primary mast cells from Mitf(-/-) mice. We found that these isoforms restored granular morphology and integrin-mediated migration. By microarray analysis, proteases, signaling molecules, cell surface receptor, and transporters comprised the largest groups of genes up-regulated by all isoforms. Furthermore, we found that isoforms also regulated distinct genes sets, suggesting separable biological activities. This work defines the transcriptome regulated by Mitf in mast cells and supports its role as master regulator of mast cell differentiation. Expression of multiple isoforms of this transcription factor may provide for redundancy of biological activities while also allowing diversity of function.
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PMID:Distinct and shared transcriptomes are regulated by microphthalmia-associated transcription factor isoforms in mast cells. 1718 76

The microphthalmia-associated transcription factor (MITF) gene encodes a basic helix-loop-helix and leucin zipper protein. In this study, we identified a novel MITF isoform, MITF-CM, which possesses a unique amino terminus. Exon 1CM is located 84 kb upstream of the exon encoding the B1b domain. MITF-CM was expressed in the human mast cell line HMC-1, the human basophilic cell line KU812, and CB-derived mast cells cultured for 10 weeks as well as bone marrow mononuclear cells. Transient transfection of MITF-CM cDNA in COS-7 cells resulted in the expression of a 64-kDa protein, detected by Western blotting, and nuclear localization of the protein, detected by immunostaining. The transient cotransfection of a luciferase construct under the control of the tyrosinase promoter and MITF-CM cDNA increased luciferase activity threefold. In contrast, none of the MITF isoforms transactivated both the tryptase and chymase gene promoters, indicating differences in the gene transactivation system between humans and mice.
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PMID:MITF-CM, a newly identified isoform of microphthalmia-associated transcription factor, is expressed in cultured mast cells. 1828 17