Document Detail


Jun and JunD-dependent functions in cell proliferation and stress response.
MedLine Citation:
PMID:  20300111     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A Meixner; F Karreth; L Kenner; J M Penninger; E F Wagner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-19
Journal Detail:
Title:  Cell death and differentiation     Volume:  17     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1409-19     Citation Subset:  IM    
Affiliation:
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animal Structures / abnormalities,  metabolism,  pathology
Animals
Antioxidants / pharmacology
Cell Aging / drug effects,  genetics
Cell Proliferation* / drug effects
Cyclin D1 / genetics,  metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Embryo, Mammalian / abnormalities,  metabolism,  pathology
Epidermal Growth Factor / pharmacology
Fibroblasts / metabolism,  pathology
Gene Expression / drug effects,  genetics
Heart Defects, Congenital / genetics,  pathology
Hepatocytes / cytology,  metabolism
Hydrogen Peroxide / metabolism
Liver / metabolism,  pathology
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
NF-E2-Related Factor 2 / genetics
Nuclear Respiratory Factor 1 / genetics
Oxidative Stress* / genetics
Proto-Oncogene Proteins / genetics,  metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
Receptor, Epidermal Growth Factor / genetics
Signal Transduction / drug effects,  physiology*
Tumor Suppressor Protein p53 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Ccnd1 protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/NF-E2-Related Factor 2; 0/Nfe2l2 protein, mouse; 0/Nrf1 protein, mouse; 0/Nuclear Respiratory Factor 1; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-jun; 0/Tumor Suppressor Protein p53; 0/junD protein, mouse; 136601-57-5/Cyclin D1; 62229-50-9/Epidermal Growth Factor; 7722-84-1/Hydrogen Peroxide; EC 2.7.10.1/EGFR protein, mouse; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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