title: AP-2alpha Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes.
abstract: AP-2alpha and 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 the c-myc gene. 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 of c-myc These results suggest that the negative regulation of AP-2 on c-MYC activity was achieved through binding of AP-2 protein to the c-myc gene. 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.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hitchler
authors.forename: Wenqing
authors.initials: W
authors.lastname: Sun
authors.forename: Ehab H
authors.initials: EH
authors.lastname: Sarsour
authors.forename: Prabhat C
authors.initials: PC
authors.lastname: Goswami
authors.forename: Aloysius J
authors.initials: AJ
authors.lastname: Klingelhutz
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann