ArticleOncogene2008
Oncogenic Ras upregulates NADPH oxidase 1 gene expression through MEK-ERK-dependent phosphorylation of GATA-6.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 119 citations in OpenAlex.
- Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Purinergic Receptor Antagonists Inhibit Hemolysis Induced byPathogens (Basel, Switzerland) · 2024Article
- Targeting ROS production through inhibition of NADPH oxidases.Nature chemical biology · 2023Article
- The Contribution of Oxidative Stress toAntioxidants (Basel, Switzerland) · 2023Review
- NADPH oxidase mediated oxidative stress signaling in FLT3-ITD acute myeloid leukemia.Cell death discovery · 2023Review
- Low dose radiation upregulates Ras/p38 and NADPH oxidase in mouse colon two months after exposure.Molecular biology reports · 2023Article
- Targeting Ferroptosis Pathway to Combat Therapy Resistance and Metastasis of Cancer.Frontiers in pharmacology · 2022Review
- The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis.Oncogene · 2021Article
- CUT Domain Proteins in DNA Repair and Cancer.Cancers · 2021Review
- Cross-Talk between Oxidative Stress and mOxidative medicine and cellular longevity · 2021Review
- The Promoting Effect of Traumatic Brain Injury on the Incidence and Progression of Glioma: A Review of Clinical and Experimental Research.Journal of inflammation research · 2021Review
- EmergingGenes · 2020Review
- Current updates on the role of reactive oxygen species in bladder cancer pathogenesis and therapeutics.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Ferroptosis in Cancer Cell Biology.Cancers · 2020Review
- A Novel STAT3-Mediated GATA6 Pathway Contributes toOxidative medicine and cellular longevity · 2020Article
- Oxidative Damage and Antioxidant Defense in Ferroptosis.Frontiers in cell and developmental biology · 2020Review
- The transition from local to global patterns governs the differentiation of mouse blastocysts.PloS one · 2020Article
- Cysteine-based regulation of redox-sensitive Ras small GTPases.Redox biology · 2019Review
- NF-κB-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells.Oncogene · 2019Article
- Subverted regulation of Nox1 NADPH oxidase-dependent oxidant generation by protein disulfide isomerase A1 in colon carcinoma cells with overactivated KRas.Cell death & disease · 2019Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ras oncogene upregulates the expression of nicotinamide adenine dinucleotide phosphate oxidase (Nox) 1 via the Raf/MEK/ERK pathway, leading to the elevated production of reactive oxygen species that is essential for maintenance of Ras-transformation phenotypes. However, the precise transcriptional control mechanism underlying Ras-induced Nox1 expression remains to be elucidated. Here we demonstrated that via the MEK/ERK pathway, Ras signaling enhances the activity of the functional Nox1 promoter (nt -321 to -1) in colon cancer CaCo-2 cells and thereby induces the formation of the specific protein-DNA complexes in the two GATA-binding site-containing regions (nt -161 to -136 and -125 to -100). Supershift assays with GATA antibodies, protein analyses and chromatin immunoprecipitation revealed that GATA-6 is a component of the specific protein-DNA complexes at the Nox1 promoter. GATA-6 was able to trans-activate the Nox1 promoter but not a promoter in which the GATA-binding sites are mutated. Moreover, GATA-6 was phosphorylated at serine residues by MEK-activated ERK, which increased GATA-6 DNA binding, correlating with suppression of the Nox1 promoter activity by an MEK inhibitor PD98059. Finally, the site-directed mutation of the consensus ERK phosphorylation site (PYS(120)P to PYA(120)P) of GATA-6 abolished its trans-activation activity, suppressing of the growth of CaCo-2 cells. On the basis of these results, we propose that oncogenic Ras signaling upregulates the transcription of Nox1 through MEK-ERK-dependent phosphorylation of GATA-6.
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