ArticleEnvironmental health perspectives2008
A novel role of the NRF2 transcription factor in the regulation of arsenite-mediated keratin 16 gene expression in human keratinocytes.
Article in Environmental health perspectives, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 34 citations in OpenAlex.
- BarH-like homeobox 2 represses the transcription of keratin 16 and affects Ras signaling pathway to suppress nasopharyngeal carcinoma progression.Bioengineered · 2022Article
- p62 functions as a signal hub in metal carcinogenesis.Seminars in cancer biology · 2021Review
- Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis.International journal of molecular sciences · 2020Review
- Altered keratinocyte differentiation is an early driver of keratin mutation-based palmoplantar keratoderma.Human molecular genetics · 2019Article
- Glucose starvation induces LKB1-AMPK-mediated MMP-9 expression in cancer cells.Scientific reports · 2018Article
- Implication of KRT16, FAM129A and HKDC1 genes as ATF4 regulated components of the integrated stress response.PloS one · 2018Article
- PML-Nuclear Bodies Regulate the Stability of the Fusion Protein Dendra2-Nrf2 in the Nucleus.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018Article
- Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes.The Journal of clinical investigation · 2016Article
- Coordinated regulation of Nrf2 and histone H3 serine 10 phosphorylation in arsenite-activated transcription of the human heme oxygenase-1 gene.Biochimica et biophysica acta · 2015Article
- Keratin 16 regulates innate immunity in response to epidermal barrier breach.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Arsenic inhibits autophagic flux, activating the Nrf2-Keap1 pathway in a p62-dependent manner.Molecular and cellular biology · 2013Article
- In Vivo Effect of Arsenic Trioxide on Keap1-p62-Nrf2 Signaling Pathway in Mouse Liver: Expression of Antioxidant Responsive Element-Driven Genes Related to Glutathione Metabolism.ISRN hepatology · 2013Article
- Article
- Oxidative stress, Nrf2 and keratin up-regulation associate with Mallory-Denk body formation in mouse erythropoietic protoporphyria.Hepatology (Baltimore, Md.) · 2012Article
- Differential modulation of keratin expression by sulforaphane occurs via Nrf2-dependent and -independent pathways in skin epithelia.Molecular biology of the cell · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInorganic sodium arsenite (iAs) is a ubiquitous environmental contaminant and is associated with an increased risk of skin hyperkeratosis and cancer.
objectivesWe investigated the molecular mechanisms underlying the regulation of the keratin 16 (K16) gene by iAs in the human keratinocyte cell line HaCaT.
methodsWe performed reverse transcriptase polymerase chain reaction, luciferase assays, Western blots, and electrophoretic mobility shift assays to determine the transcriptional regulation of the K16 gene by iAs. We used gene overexpression approaches to elucidate the nuclear factor erythroid-derived 2 related factor 2 (NRF2) involved in the K16 induction.
resultsiAs induced the mRNA and protein expression of K16. We also found that the expression of K16 was transcriptionally induced by iAs through activator protein-1-like sites and an antioxidant response element (ARE) in its gene promoter region. Treatment with iAs also enhanced the production and translocation of the NRF2 transcription factor, an ARE-binding protein, into the nucleus without modification of its mRNA expression. In addition, iAs elongated the half-life of the NRF2 protein. When overexpressed in HaCaT cells, NRF2 was also directly involved in not only the up-regulation of the detoxification gene thioredoxin but also K16 gene expression.
conclusionsOur data clearly indicate that the K16 gene is a novel target of NRF2. Furthermore, our findings also suggest that NRF2 has opposing roles in the cell--in the activation of detoxification pathways and in promoting the development of skin disorders.
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