Heterodimerization with different Jun proteins controls c-Fos intranuclear dynamics and distribution.

Abstract : The c-Fos proto-oncogenic transcription factor defines a multigene family controlling many processes both at the cell and the whole organism level. To bind to its target AP-1/TRE or CRE DNA sequences in gene promoters and exert its transcriptional part, c-Fos must heterodimerize with other bZip proteins, its best studied partners being the Jun proteins (c-Jun, JunB and JunD). c-Fos expression is regulated at many transcriptional and post-transcriptional levels. Yet, little is known on how its localization is dynamically regulated in the cell. We have investigated here its intranuclear mobility using FRAP-, genetic- and biochemical approaches. Whereas monomeric c-Fos is highly mobile and distributed evenly with nucleolar exclusion in the nucleus, heterodimerization with c-Jun entails intranuclear redistribution and dramatic reduction in mobility of c-Fos due to predominant association with the nuclear matrix independently of any binding to AP-1/TRE or CRE sequences. In contrast to c-Jun, dimerization with JunB does not detectably affect c-Fos mobility. However, dimerization with JunB affects intranuclear distribution with significant differences in the localization of c-Fos:c-Jun and c-Fos:JunB dimers. Moreover, c-Jun and JunB exert comparable effects on another Fos family member, Fra-1. Thus, we report a novel regulation, i.e. differentially regulated intranuclear mobility and distribution of Fos proteins by their Jun partners, and suggest the existence of intranuclear storage sites for latent c-Fos:c-Jun AP-1 complexes. This may affect the numerous physiopathological functions these transcription factors control.
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Contributor : Cyril Favard <>
Submitted on : Tuesday, February 9, 2010 - 6:15:41 PM
Last modification on : Monday, March 4, 2019 - 2:04:12 PM

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Cecile E Malnou, Frederique Brockly, Cyril Favard, Gabriel Moquet-Torcy, Marc Piechaczyk, et al.. Heterodimerization with different Jun proteins controls c-Fos intranuclear dynamics and distribution.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, epub ahead of print. ⟨10.1074/jbc.M109.032680⟩. ⟨hal-00455236⟩

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