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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

Authors

  • Meixner A
  • Karreth F
  • Kenner L
  • Penninger JM
  • Wagner EF

Journal

Cell death and differentiation

Publication Data

September 16, 2010

Associated Grants

None

Mesh Terms

  • 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