JunD Reduces Tumor Angiogenesis by Protecting Cells from Oxidative Stress
Open accessAbstract
Reactive oxygen species (ROS) are implicated in the pathophysiology of various diseases, including cancer. In this study, we show that JunD, a member of the AP-1 family of transcription factors, reduces tumor angiogenesis by limiting Ras-mediated production of ROS. Using junD-deficient cells, we demonstrate that JunD regulates genes involved in antioxidant defense, H2O2 production, and angiogenesis. The accumulation of H2O2 in junD-/- cells decreases the availability of FeII and reduces the activity of HIF prolyl hydroxylases (PHDs) that target hypoxia-inducible factors-alpha (HIFalpha) for degradation. Subsequently, HIF-alpha proteins accumulate and enhance the transcription of VEGF-A, a potent proangiogenic factor. Our study uncovers the mechanism by which JunD protects cells from oxidative stress and exerts an antiangiogenic effect. Furthermore, we provide new insights into the regulation of PHD activity, allowing immediate reactive adaptation to changes in O2 or iron levels in the cell.
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Tf bound with iron releases iron at acidic pH because of major conformational changes including a 54- to 63-degree rotation between the two domains on each lobe.
“Tf bound with iron releases iron at acidic pH because of major conformational changes including a 54- to 63-degree rotation between the two domains on each lobe (103).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [103]
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Wilkes, J. G., O’Leary, B. R., Du, J., Klinger, A. R., Sibenaller, Z. A., Doskey, C. M., Gibson-Corley, K. N., Alexander, M. S., Tsai, S., Buettner, G. R., et al. (2018) · Clinical & Experimental Metastasis · doi:10.1007/s10585-018-9876-z · Cited by 36 · see citing works
Histone H2AX deficiency causes neurobehavioral deficits and impaired redox homeostasis
Weyemi, U., Paul, B. D., Snowman, A. M., Jailwala, P., Nussenzweig, A., Bonner, W. M., & Snyder, S. H. (2018) · Nature Communications · doi:10.1038/s41467-018-03948-9 · Cited by 37 · see citing works
Collaboration between mitochondria and the nucleus is key to long life in Caenorhabditis elegans
Chang, H.-W., Shtessel, L., & Lee, S. S. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.576 · Cited by 15 · see citing works
- Authors
- Gerald, D., Berra, E., Frapart, Y. M., Chan, D. A., Giaccia, A. J., Mansuy, D., Pouysségur, J., Yaniv, M., & Mechta-Grigoriou, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Stanford Medicine (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 118
- Issue
- 6
- Pages
- 781-794
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1963545628
- Cited by
- 588
- References
- 60
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 19 · 2023: 18 · 2022: 14 · 2021: 27 · 2020: 10 · 2019: 20 · 2018: 15 · 2017: 15 · 2016: 25 · 2015: 25 · 2014: 36 · 2013: 33 · 2012: 32
- FWCI
- 13.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3241 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- JunD, tumor angiogenesis, oxidative stress, reactive oxygen species, AP-1 transcription factor, Ras signaling, hydrogen peroxide, HIF prolyl hydroxylase, hypoxia, VEGF-A, antioxidant defense, iron availability, antiangiogenic activity
- MeSH terms
- Animals, Antioxidants, Humans, Hydrogen Peroxide, Iron, Neoplasms, Neovascularization, Pathologic, Procollagen-Proline Dioxygenase, Transcription Factors, Up-Regulation, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-jun, Reactive Oxygen Species, Oxidative Stress, ras Proteins, Vascular Endothelial Growth Factor A, Dioxygenases, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia-Inducible Factor-Proline Dioxygenases
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