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

Han Liu, Xuehong Deng, Y. John Shyu, Jian-Jian Li, Elizabeth J. Taparowsky, Chang Deng Hu

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1058-1069
Number of pages12
JournalEMBO Journal
Volume25
Issue number5
DOIs
StatePublished - Mar 8 2006
Externally publishedYes

Keywords

  • ATF2
  • BiFC
  • c-Jun
  • Differentiation
  • NES

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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