TY - JOUR
T1 - JunD protects cells from p53-dependent senescence and apoptosis
AU - Weitzman, Jonathan B.
AU - Fiette, Laurence
AU - Matsuo, Koichi
AU - Yaniv, Moshe
N1 - Funding Information:
We are grateful to members of the Yaniv laboratory for helpful discussions and advice. In addition, we thank all those who provided valuable reagents. J. B. W. thanks Evelyne Bois for technical assistance and Cipi Gawer-Weitzman for encouragement. This work was supported by the Association pour la Recherche contre le Cancer (ARC), EC Biomed and Training and Mobility of Researchers (TMR) Programs, and the Association for International Cancer Research (AICR).
PY - 2000
Y1 - 2000
N2 - 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-α. The anti-apoptotic 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.
AB - 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-α. The anti-apoptotic 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.
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U2 - 10.1016/S1097-2765(00)00109-X
DO - 10.1016/S1097-2765(00)00109-X
M3 - Article
C2 - 11106750
AN - SCOPUS:0033634878
SN - 1097-2765
VL - 6
SP - 1109
EP - 1119
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -
