Mutual regulation of c-Jun and ATF2 by transcriptional activation and subcellular localization

被引:96
作者
Liu, H
Deng, XH
Shyu, YJ
Li, JJ
Taparowsky, EJ
Hu, CD
机构
[1] Purdue Univ, Sch Pharm, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA
[2] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA
[3] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA
[4] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA
[5] Walther Canc Inst, Indianapolis, IN USA
关键词
ATF2; BiFC; c-jun; differentiation; NES;
D O I
10.1038/sj.emboj.7601020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ATF2 and c-Jun are key components of activating protein-1 and function as homodimers or heterodimers. c-Jun-ATF2 heterodimers activate the expression of many target genes, including c-jun, in response to a variety of cellular and environmental signals. Although it has been believed that c-Jun and ATF2 are constitutively localized in the nucleus, where they are phosphorylated and activated by mitogen-activated protein kinases, the molecular mechanisms underlying the regulation of their transcriptional activities remain to be defined. Here we show that ATF2 possesses a nuclear export signal in its leucine zipper region and two nuclear localization signals in its basic region, resulting in continuous shuttling between the cytoplasm and the nucleus. Dimerization with c-Jun in the nucleus prevents the export of ATF2 and is essential for the transcriptional activation of the c-jun promoter. Importantly, c-Jun-dependent nuclear localization of ATF2 occurs during retinoic acid-induced differentiation and UV-induced cell death in F9 cells. Together, these findings demonstrate that ATF2 and c-Jun mutually regulate each other by altering the dynamics of subcellular localization and by positively impacting transcriptional activity.
引用
收藏
页码:1058 / 1069
页数:12
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