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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

c-Fos, a component of the transcription factor AP-1, is rapidly imported into the nucleus after translation. We established an in vitro system using digitonin-permeabilized cells to analyze nuclear import of c-Fos in detail. Two import receptors of the importin beta superfamily, importin beta itself and transportin, promote import of c-Fos in vitro. Under conditions where importin beta-dependent transport was blocked, c-Fos still accumulated in the nucleus in the presence of cytosol. Inhibition of the transportin-dependent pathway, in contrast, abolished import of c-Fos. Furthermore, c-Fos mutants that interact with transportin but not with importin beta were efficiently imported in the presence of cytosol. Hence, transportin appears to be the predominant import receptor for c-Fos. A detailed biochemical characterization revealed that the interaction of transportin with c-Fos is distinct from the interaction with its established import cargoes, the M9 sequence of heterogeneous nuclear ribonucleoprotein A1 or the nuclear localization sequence of some basic proteins. Likewise, the binding sites on importin beta for its classic import cargo and for c-Fos can be separated. In summary, c-Fos employs a novel mode of receptor-cargo interaction. Hence, transportin may be as versatile as importin beta in recognizing different nuclear import cargoes.
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PMID:Transportin is a major nuclear import receptor for c-Fos: a novel mode of cargo interaction. 1640 15

c-Jun and c-Fos are major components of the transcriptional complex AP-1. Here, we investigate the nuclear import pathway(s) of the transcription factor c-Jun. c-Jun bound specifically to the nuclear import receptors importin beta, transportin, importin 5, importin 7, importin 9, and importin 13. In digitonin-permeabilized cells, importin beta, transportin, importin 7, and importin 9 promoted efficient import of c-Jun into the nucleus. Importin alpha, by contrast, inhibited nuclear import of c-Jun in vitro. A single basic region preceding the leucine zipper of c-Jun functions as a nuclear localization signal (NLS) and was required for interaction with all tested import receptors. In vivo, nuclear import of a c-Jun reporter protein lacking the leucine zipper strictly depended on this NLS. In a leucine zipper-dependent manner, c-Jun with mutations in its NLS was still imported into the nucleus in a complex with endogenous leucine zipper proteins or, for example, with cotransfected c-Fos. Together, these results explain the highly efficient nuclear import of the transcription factor c-Jun.
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PMID:Nuclear import of c-Jun is mediated by multiple transport receptors. 1765 81

c-Fos proto-oncoprotein forms AP-1 transcription complexes with heterodimerization partners such as c-Jun, JunB, and JunD. Thereby, it controls essential cell functions and exerts tumorigenic actions. The dynamics of c-Fos intracellular distribution is poorly understood. Hence, we have combined genetic, cell biology, and microscopic approaches to investigate this issue. In addition to a previously characterized basic nuclear localization signal (NLS) located within the central DNA-binding domain, we identified a second NLS within the c-Fos N-terminal region. This NLS is non-classic and its activity depends on transportin 1 in vivo. Under conditions of prominent nuclear localization, c-Fos can undergo nucleocytoplasmic shuttling through an active Crm-1 exportin-independent mechanism. Dimerization with the Jun proteins inhibits c-Fos nuclear exit. The strongest effect is observed with c-Jun probably in accordance with the relative stabilities of the different c-Fos:Jun dimers. Retrotransport inhibition is not caused by binding of dimers to DNA and, therefore, is not induced by indirect effects linked to activation of c-Fos target genes. Monomeric, but not dimeric, Jun proteins also shuttle actively. Thus, our work unveils a novel regulation operating on AP-1 by demonstrating that dimerization is crucial, not only for active transcription complex formation, but also for keeping them in the compartment where they exert their transcriptional function.
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PMID:Heterodimerization with Jun family members regulates c-Fos nucleocytoplasmic traffic. 1768 51