JunD protects cells from p53-dependent senescence and apoptosis.

Abstract:

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Weitzman JB,Fiette L,Matsuo K,Yaniv M

doi

10.1016/s1097-2765(00)00109-x

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

1109-19

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(00)00109-X

journal_volume

6

pub_type

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