JunD protects cells from p53-dependent senescence and apoptosis

JunD is the most broadly expressed member of the Jun family and the AP-1 transcription factor complex. Primary fibroblasts lacking JunD displayed p53-dependent growth arrest, upregulated p19(Arf) expression, and premature senescence. In contrast, immortalized cell lines lacking JunD showed increased...

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Bibliographic Details
Published in:Molecular cell 2000-11, Vol.6 (5), p.1109-1119
Main Authors: Weitzman, J B, Fiette, L, Matsuo, K, Yaniv, M
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Apoptosis - drug effects
Apoptosis - physiology
Apoptosis - radiation effects
Cell Division - drug effects
Cell Line, Transformed
Cells, Cultured
Cellular Senescence - drug effects
Cellular Senescence - physiology
Cyclin D1 - metabolism
Cyclin-Dependent Kinase Inhibitor p16
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - metabolism
Fibroblasts - radiation effects
Gene Deletion
Hepatitis, Animal - chemically induced
Hepatitis, Animal - metabolism
Hepatitis, Animal - pathology
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - pathology
JunD gene
Lipopolysaccharides - pharmacology
Mice
Mice, Knockout
Proto-Oncogene Proteins c-jun - deficiency
Proto-Oncogene Proteins c-jun - genetics
Proto-Oncogene Proteins c-jun - metabolism
Radiation Tolerance - genetics
ras Proteins - metabolism
Signal Transduction - drug effects
Signal Transduction - radiation effects
Survival Rate
Tumor Necrosis Factor-alpha - pharmacology
Tumor Suppressor Protein p14ARF - metabolism
Tumor Suppressor Protein p53 - antagonists & inhibitors
Tumor Suppressor Protein p53 - metabolism
Ultraviolet Rays
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Summary:JunD is the most broadly expressed member of the Jun family and the AP-1 transcription factor complex. Primary fibroblasts lacking JunD displayed p53-dependent growth arrest, upregulated p19(Arf) expression, and premature senescence. In contrast, immortalized cell lines lacking JunD showed increased proliferation and higher cyclinD1 levels. These properties are reminiscent of the effects of oncogenic Ras expression on primary and established cell cultures. Furthermore, JunD(-/-) fibroblasts exhibited increased p53-dependent apoptosis upon ultraviolet irradiation and were sensitive to the cytotoxic effects of TNF-alpha. The antiapoptotic role of JunD was confirmed using an in vivo model of TNF-mediated hepatitis. We propose that JunD protects cells from senescence, or apoptotic responses to stress stimuli, by acting as a modulator of the signaling pathways that link Ras to p53.
ISSN:1097-2765
DOI:10.1016/s1097-2765(00)00109-x