Journal article
AP-2α Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes
Journal of oncology, Vol.2009, 780874
2009
DOI: 10.1155/2009/780874
PMCID: PMC2801504
PMID: 20066163
Abstract
AP-2αand c-MYC are important transcription factors involved in multiple cellular processes. They each display the paradoxical capacities to stimulate both cell proliferation and apoptosis under different conditions. In the present study we found that over expression of c-MYC was associated with accumulation of reactive oxygen species (ROS) and apoptosis in human keratinocytes, both of which were significantly inhibited by co-expression of AP-2. The effects of AP-2 on c-MYC were active at several levels. First, AP-2 and c-MYC were confirmed to interact at the protein level as previously described. In addition, forced expression of AP-2 significantly decreased steady state levels of c-MYC mRNA and protein. These findings suggested that AP-2 may have a direct effect on thec-mycgene. Chromatin immunoprecipitation assays demonstrated that AP-2 proteins bound to a cluster of AP-2 binding sites located within a 2 kb upstream regulatory region ofc-mycThese results suggest that the negative regulation of AP-2 on c-MYC activity was achieved through binding of AP-2 protein to thec-mycgene. The effects of AP-2 on c-MYC induced ROS accumulation and apoptosis in epidermal keratinocytes are likely to play an important role in cell growth, differentiation and carcinogenesis of the skin.
Details
- Title: Subtitle
- AP-2α Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes
- Creators
- Lei Yu - Free Radical & Radiation Biology Graduate Program, Radiation Oncology Department, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAMichael J Hitchler - Free Radical & Radiation Biology Graduate Program, Radiation Oncology Department, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAWenqing Sun - Free Radical & Radiation Biology Graduate Program, Radiation Oncology Department, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAEhab H Sarsour - Free Radical & Radiation Biology Graduate Program, Radiation Oncology Department, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAPrabhat C Goswami - Free Radical & Radiation Biology Graduate Program, Radiation Oncology Department, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAAloysius J Klingelhutz - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAFrederick E Domann - Free Radical & Radiation Biology Graduate Program, Radiation Oncology Department, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Journal of oncology, Vol.2009, 780874
- DOI
- 10.1155/2009/780874
- PMID
- 20066163
- PMCID
- PMC2801504
- NLM abbreviation
- J Oncol
- ISSN
- 1687-8450
- eISSN
- 1687-8450
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01-CA073612, R01-CA115438, R01-CA111365, R01-AG0227388, P30-CA086862
- Language
- English
- Date published
- 2009
- Academic Unit
- Microbiology and Immunology; Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984001139202771
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