JunD protects cells from p53-dependent senescence and apoptosis

JunD is the most broadly expressed member of the Jun family and the AP-1 tr anscription factor complex. Primary fibroblasts lacking JunD displayed p53- dependent growth arrest, upregulated p19(Arf) expression, and premature sen escence. In contrast, immortalized cell lines lacking JunD showed increased proliferation and higher cyclinD1 levels. These properties are reminiscent of the effects of oncogenic Pas expression on primary and established cell cultures. Furthermore, JunD(-/-) fibroblasts exhibited increased p53-depen dent apoptosis upon ultraviolet irradiation and were sensitive to the cytot oxic effects of TNF-alpha. The anti-apoptotic role of JunD was confirmed us ing an in vivo model of TNF-mediated hepatitis. We propose that JunD protec ts cells from senescence, or apoptotic responses to stress stimuli, by acti ng as a modulator of the signaling pathways that link Pas to p53.