NADPH oxidase 1 (Nox1) is a multicomponent enzyme consisting of p22(phox), Nox organizer 1 (NOXO1), Nox1 activator 1, and Rac1. Interleukin-1beta, flagellin, interferon-gamma, and tumor necrosis factor alpha (TNF-alpha) similarly induced Nox1 in a colon cancer cell line (T84), whereas only TNF-alpha fully induced NOXO1 and upregulated superoxide-producing activity by ninefold. This upregulation was canceled by knockdown of NOXO1 with small interfering RNAs. TNF-alpha rapidly phosphorylated p38 mitogen-activated protein kinase and c-Jun N-terminal kinase 1/2, followed by phosphorylation of c-Jun and c-Fos and appearance of an AP-1 binding activity within 30 min. We cloned the 5' flank of the human NOXO1 gene (-3888 to +263 bp), and found that the region between -585 and -452 bp, which contains consensus elements of YY-1, AP-1, and Ets, and the GC-rich region encoding three putative binding sites for SP-1, was crucial for TNF-alpha-dependent promoter activity. Serial mutation analysis of the elements identified an AP-1 binding site (from -561 to -551 bp, agtAAGtcatg) as a crucial element for TNF-alpha-stimulated transcription of the human NOXO1 gene, which was also confirmed by the AP-1 decoy experiments. Thus, TNF-alpha acts as a potent activator of Nox1-based oxidase in colon epithelial cells, suggesting a potential role of this oxidase in inflammation of the colon.
NADPH oxidase 1 ( Nox1 ) is a multicomponent enzyme consisting of p22(phox ) , Nox organizer 1 ( NOXO1 ) , Nox1 activator 1 , and Rac1 . Interleukin-1beta , flagellin , interferon - gamma , and tumor necrosis factor alpha ( TNF - alpha ) similarly induced Nox1 in a colon cancer cell line ( T84 ) , whereas only TNF - alpha fully induced NOXO1 and upregulated superoxide - producing activity by ninefold . This upregulation was canceled by knockdown of NOXO1 with small interfering RNAs . TNF - alpha rapidly phosphorylated p38 mitogen - activated protein kinase and c - Jun N - terminal kinase 1/2 , followed by phosphorylation of c - Jun and c - Fos and appearance of an AP-1 binding activity within 30 min . We cloned the 5 ' flank of the human NOXO1 gene ( -3888 to +263 bp ) , and found that the region between -585 and -452 bp , which contains consensus elements of YY-1 , AP-1 , and Ets , and the GC - rich region encoding three putative binding sites for SP-1 , was crucial for TNF - alpha - dependent promoter activity . Serial mutation analysis of the elements identified an AP-1 binding site ( from -561 to -551 bp , agtAAGtcatg ) as a crucial element for TNF - alpha - stimulated transcription of the human NOXO1 gene , which was also confirmed by the AP-1 decoy experiments . Thus , TNF - alpha acts as a potent activator of Nox1-based oxidase in colon epithelial cells , suggesting a potential role of this oxidase in inflammation of the colon .
Which NADPH oxidase family member requires interaction with NOXO1 for function?
Which NADPH oxidase family member requires interaction with NOXO1 for function ?
NADPH oxidase 1 NOX1
NADPH oxidase 1 NOX1 nicotinamide adenine dinucleotide phosphate-oxidase 1