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

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.

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