Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gp91(phox) gene encodes a component of the respiratory burst NADPH oxidase complex and is highly expressed in mature myeloid cells. The transcriptional repressor CCAAT displacement protein binds to at least five sites within the proximal gp91(phox) promoter and represses expression prior to terminal phagocyte differentiation. The DNA binding activity of CCAAT displacement protein decreases during terminal phagocyte differentiation, thus permitting the binding of transcriptional activators and induction of gp91(phox) expression. We report here that the matrix attachment region-binding protein SATB1 interacts with at least seven sites within the -1542 to +12-base pair gp91(phox) promoter. Four additional binding sites for CCAAT displacement protein were also identified. Furthermore, the most proximal SATB1-binding site within the gp91(phox) promoter binds specifically to the nuclear matrix fraction in vitro. SATB1 expression is down-regulated during terminal myeloid cell differentiation, coincident with induction of gp91(phox) expression. Transient transfection assays demonstrate that a SATB1-binding site derived from the gp91(phox) promoter represses promoter activity in cells expressing SATB1. These findings underscore the importance of transcriptional repression in the regulation of gp91(phox) expression and reveal a candidate myeloid cell target gene for SATB1, a factor previously found to be essential for T cell development.
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PMID:The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation. 1157 75

The expression of gp91(phox), the key component of the phagocyte NADPH oxidase, is regulated by various factors binding to its proximal promoter. Two nuclear matrix attachment region (MAR)-binding proteins, special AT-rich binding protein 1 (SATB1) and CCAAT displacement protein (CDP), have been reported as rare examples of gp91(phox) gene repressors. However, their individual roles and interactions with other factors in the promoter have not been elucidated in detail. We have focused on these two repressive proteins recognizing the bp -115 to bp -106 segment of the gene and obtained the following results: 1. SATB1 makes a complex, mainly with p300, regardless of the presence of DNA. 2. SATB1/p300 complex binding to the 5' upstream AT-rich region in the bp -115 to bp -106 segment represses the gp91(phox) promoter activity, and the repressed activity is partially released by CDP binding to the CCAAT element directly downstream of the AT-rich region. Our findings imply a novel role for p300 in SATB1-associated global transcription regulation.
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PMID:SATB1 makes a complex with p300 and represses gp91(phox) promoter activity. 1460 47

Infection of neutrophil precursors with Anaplasma phagocytophilum, the causative agent of human granulocytic ehrlichiosis, results in downregulation of the gp91(phox) gene, a key component of NADPH oxidase. We now show that repression of gp91(phox) gene transcription is associated with reduced expression of interferon regulatory factor 1 (IRF-1) and PU.1 in nuclear extracts of A. phagocytophilum-infected cells. Loss of PU.1 and IRF-1 correlated with increased binding of the repressor, CCAAT displacement protein (CDP), to the promoter of the gp91(phox) gene. Reduced protein expression of IRF-1 was observed with or without gamma interferon (IFN-gamma) stimulation, and the defect in IFN-gamma signaling was associated with diminished binding of phosphorylated Stat1 to the Stat1 binding element of the IRF-1 promoter. The diminished levels of activator proteins and enhanced binding of CDP account for the transcriptional inhibition of the gp91(phox) gene during A. phagocytophilum infection, providing evidence of the first molecular mechanism that a pathogen uses to alter the regulation of genes that contribute to an effective respiratory burst.
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PMID:Anaplasma phagocytophilum modulates gp91phox gene expression through altered interferon regulatory factor 1 and PU.1 levels and binding of CCAAT displacement protein. 1561 56