Human Proteinase-3 Expression Is Regulated by PU.1 in Conjunction with a Cytidine-rich Element
| Autor: | Kerry F. Franklin, Anne Sturrock, John R. Hoidal |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Cathepsin G
Myeloblastin Molecular Sequence Data Cytidine Biology Autoantigens Biochemistry Gene Expression Regulation Enzymologic chemistry.chemical_compound Azurophilic granule Proto-Oncogene Proteins Gene expression Humans Nuclear protein Promoter Regions Genetic Molecular Biology Sequence Deletion Base Sequence Molecular mass Serine Endopeptidases Elastase Granulomatosis with Polyangiitis Cell Differentiation Promoter Cell Biology Cathepsins Molecular biology chemistry Trans-Activators Tetradecanoylphorbol Acetate Leukocyte Elastase |
| Zdroj: | Journal of Biological Chemistry. 271:32392-32402 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.50.32392 |
| Popis: | Human proteinase-3 is one of three serine proteinases present in the azurophil granules of polymorphonuclear leukocytes along with elastase and cathepsin G. Proteinase-3 gene expression is confined to the promyelocytic stage of polymorphonuclear leukocyte maturation. The present investigation identifies elements responsible for this highly controlled tissue- and developmental-specific expression of proteinase-3. Within the first 200 base pairs of the proteinase-3 promoter, two elements were identified as important for expression, these elements at −101 and −190 confer the majority of the activity. The element at −101 has a PU.1 consensus. It binds a myeloid nuclear protein of approximately 45 kDa that “supershifts” with PU.1 antibody and is competed by the CD11b PU.1 element. The element at −190 has a core sequence of CCCCGCCC (CG element). The cytidines but not the guanidine are essential for promoter activity. The CG element binds a second nuclear protein with a molecular mass of approximately 40 kDa that is found in cells of myeloid lineage as well as non-myeloid HeLa cells. However, the proteinase-3 promoter is not active in HeLa cells which suggests that the CG element alone is not sufficient for proteinase-3 gene expression. Maturation of promyelocytic cells results in an inhibition of proteinase-3 gene expression and a reduction in nuclear protein binding to the PU.1 and CG elements. Similar elements occur in the elastase and cathepsin G promoters. Using the elastase and cathepsin G PU.1 and CG-like elements as probes results in identical band-shift patterns to that obtained with proteinase-3 PU.1 and CG elements. These data suggest that there is cooperative interaction between a PU.1 and a CG element with a consensus of CCCCXCCC and that they are important control elements for tissue- and developmental-specific expression of azurophil serine proteinases of polymorphonuclear leukocytes. |
| Databáze: | OpenAIRE |
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