ArticleThe Journal of biological chemistry2014
Negative regulation of NADPH oxidase 4 by hydrogen peroxide-inducible clone 5 (Hic-5) protein.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Hic-5 drives epithelial mechanotransduction promoting a feed-forward cycle of bronchoconstriction.Nature communications · 2025Article
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- Friend or foe? The elusive role of hepatic stellate cells in liver cancer.Nature reviews. Gastroenterology & hepatology · 2023Review
- Spatial resolution of cellular senescence dynamics in human colorectal liver metastasis.Aging cell · 2023Article
- Article
- Mitochondrial uncoupling protein-2 reprograms metabolism to induce oxidative stress and myofibroblast senescence in age-associated lung fibrosis.Aging cell · 2022Article
- Reactive Oxygen Species and Oxidative Stress in Vascular-Related Diseases.Oxidative medicine and cellular longevity · 2022Review
- Connexin32 ameliorates renal fibrosis in diabetic mice by promoting K48-linked NADPH oxidase 4 polyubiquitination and degradation.British journal of pharmacology · 2020Article
- Hydrogen peroxide inducible clone-5 sustains NADPH oxidase-dependent reactive oxygen species-c-jun N-terminal kinase signaling in hepatocellular carcinoma.Oncogenesis · 2019Article
- Role of fibroblast growth factor 23 and klotho cross talk in idiopathic pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Gene expression analysis of heat-shock proteins and redox regulators reveals combinatorial prognostic markers in carcinomas of the gastrointestinal tract.Redox biology · 2019Article
- Regulation of mitochondrial ROS production by HIC-5: a common feature of oncogene-induced senescence and tumor invasiveness?The FEBS journal · 2019Article
- A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS-activated cancer cells.The FEBS journal · 2019Article
- IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5.Mucosal immunology · 2018Article
- TRAF4 promotes lung cancer aggressiveness by modulating tumor microenvironment in normal fibroblasts.Scientific reports · 2017Article
- Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.Autophagy · 2017Article
- Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- NADPH oxidase in brain injury and neurodegenerative disorders.Molecular neurodegeneration · 2017Review
- Heat shock protein 27 plays a protective role in thoracic aortic dissection by promoting cell proliferation and inhibiting apoptosis.Cellular & molecular biology letters · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hydrogen peroxide-inducible clone 5 (Hic-5) is a focal adhesion adaptor protein induced by the profibrotic cytokine TGF-β1. We have demonstrated previously that TGF-β1 induces myofibroblast differentiation and lung fibrosis by activation of the reactive oxygen species-generating enzyme NADPH oxidase 4 (Nox4). Here we investigated a potential role for Hic-5 in regulating Nox4, myofibroblast differentiation, and senescence. In normal human diploid fibroblasts, TGF-β1 induces Hic-5 expression in a delayed manner relative to the induction of Nox4 and myofibroblast differentiation. Hic-5 silencing induced constitutive Nox4 expression and enhanced TGF-β1-inducible Nox4 levels. The induction of constitutive Nox4 protein in Hic-5-silenced cells was independent of transcription and translation and controlled by the ubiquitin-proteasomal system. Hic-5 associates with the ubiquitin ligase Cbl-c and the ubiquitin-binding protein heat shock protein 27 (HSP27). The interaction of these proteins is required for the ubiquitination of Nox4 and for maintaining low basal levels of this reactive oxygen species-generating enzyme. Our model suggests that TGF-β1-induced Hic-5 functions as a negative feedback mechanism to limit myofibroblast differentiation and senescence by promoting the ubiquitin-proteasomal system-mediated degradation of Nox4. Together, these studies indicate that endogenous Hic-5 suppresses senescence and profibrotic activities of myofibroblasts by down-regulating Nox4 protein expression. Additionally, these are the first studies, to our knowledge, to demonstrate posttranslational regulation of Nox4.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.