NDLI: Control of cell cycle progression by c-Jun is p53 dependent

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Control of cell cycle progression by c-Jun is p53 dependent

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Control of cell cycle progression by c-Jun is p53 dependent

Content Provider	PubMed Central
Author	Schreiber, Martin Kolbus, Andrea Piu, Fabrice Axel, Szabowski Uta, Möhle-steinlein Tian, Jianmin Karin, Michael Angel, Peter Wagner, Erwin F.
Copyright Year	1999
Abstract	The c-jun proto-oncogene encodes a component of the mitogen-inducible immediate–early transcription factor AP-1 and has been implicated as a positive regulator of cell proliferation and G1-to-S-phase progression. Here we report that fibroblasts derived from c-jun −/− mouse fetuses exhibit a severe proliferation defect and undergo a prolonged crisis before spontaneous immortalization. The cyclin D1- and cyclin E-dependent kinases (CDKs) and transcription factor E2F are poorly activated, resulting in inefficient G1-to-S-phase progression. Furthermore, the absence of c-Jun results in elevated expression of the tumor suppressor gene p53 and its target gene, the CDK inhibitor p21, whereas overexpression of c-Jun represses p53 and p21 expression and accelerates cell proliferation. Surprisingly, protein stabilization, the common mechanism of p53 regulation, is not involved in up-regulation of p53 in c-jun −/− fibroblasts. Rather, c-Jun regulates transcription of p53 negatively by direct binding to a variant AP-1 site in the p53 promoter. Importantly, deletion of p53 abrogates all defects of cells lacking c-Jun in cell cycle progression, proliferation, immortalization, and activation of G1 CDKs and E2F. These results demonstrate that an essential, rate-limiting function of c-Jun in fibroblast proliferation is negative regulation of p53 expression, and establish a mechanistic link between c-Jun-dependent mitogenic signaling and cell-cycle regulation.
Starting Page	607
File Format	PDF
ISSN	08909369
Journal	Genes & Development
Issue Number	5
Volume Number	13
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	1999-03-01
Access Restriction	Open
Rights Holder	Cold Spring Harbor Laboratory Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Developmental Biology

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