Jun and JunD-dependent functions in cell proliferation and stress response.
Jun is essential for fetal development, as fetuses lacking Jun die at mid-gestation with multiple cellular defects in liver and heart. Embryos expressing JunD in place of Jun (Jun(d/d)) can develop to term with normal fetal livers, but display cardiac defects as observed in fetuses lacking Jun. Jun(d/d) mouse embryonic fibroblasts (MEFs) exhibit early senescence, which can be rescued by EGF and HB-EGF stimulation, probably through activation of Akt signaling. Thus, JunD cannot functionally replace Jun in regulating fibroblast proliferation. In Jun(-/-) fetal livers, increased hydrogen peroxide levels are detected and expression of Nrf1 and Nrf2 (nuclear erythroid 2-related transcription factors) is downregulated. Importantly, increased oxidative stress as well as expression of Nrf1 and Nrf2 is rescued by JunD in Jun(d/d) fetal livers. These data show that Jun is of critical importance for cellular protection against oxidative stress in fetal livers and fibroblasts, and Jun-dependent cellular senescence can be restored by activation of the epidermal growth factor receptor pathway.
Pubmed ID: 20300111 RIS Download
Animal Structures | Animals | Antioxidants | Cell Aging | Cell Proliferation | Cyclin D1 | Cyclin-Dependent Kinase Inhibitor p21 | Embryo, Mammalian | Epidermal Growth Factor | Fibroblasts | Gene Expression | Heart Defects, Congenital | Hepatocytes | Hydrogen Peroxide | Liver | Mice | Mice, 129 Strain | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | NF-E2-Related Factor 2 | Nuclear Respiratory Factor 1 | Oxidative Stress | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt | Proto-Oncogene Proteins c-jun | Receptor, Epidermal Growth Factor | Signal Transduction | Tumor Suppressor Protein p53