Intramolecular inhibition of activating transcription factor-2 function by its DNA-binding domain
Howard Hughes Medical Institute; Program in Molecular Medicine; Program in Gene Function and Expression
Activating Transcription Factor 2; Animals; Cells, Cultured; Chromatography, Affinity; Cyclic AMP Response Element-Binding Protein; inhibitors; DNA Mutational Analysis; Fungal Proteins; *Gene Expression Regulation; Humans; *Leucine Zippers; Protein Binding; Recombinant Fusion Proteins; *Saccharomyces cerevisiae Proteins; Sequence Deletion; Structure-Activity Relationship; Transcription Factors; *Transcription, Genetic; Transfection
Life Sciences | Medicine and Health Sciences
ATF-2 is a cellular basic region-leucine zipper (bZIP) transcription factor that can mediate diverse transcriptional responses, including activation by the adenovirus Ela protein. ATF-2 contains an activation domain, required for transcriptional activity, but in the absence of an appropriate inducer, full-length ATF-2 is transcriptionally inactive. Here we have investigated the mechanism underlying this regulated inhibition of ATF-2 transcriptional activity. We show that the region of ATF-2 that suppresses the activation region is the bZIP DNA-binding domain and that maximal inhibition requires both the basic region and leucine zipper subdomains. Inhibition is activation domain specific: The ATF-2 bZIP suppresses the ATF-2 and the related Ela activation domains but not acidic- and glutamine-rich activation domains. In vitro protein interaction assays demonstrate that the ATF-2 activation domain and bZIP specifically bind to one another. Finally, we show that bZIP-mediated inhibition can be modulated in a cell-type-specific manner by another sequence element within ATF-2. On the basis of these and other data, we propose that the ATF-2 bZIP and activation domain are engaged in an inhibitory intramolecular interaction and that inducers of ATF-2 disrupt this interaction to activate transcription.
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Citation: Genes Dev. 1996 Mar 1;10(5):517-27.
Genes and development
Li, Xiao-Yong and Green, Michael R., "Intramolecular inhibition of activating transcription factor-2 function by its DNA-binding domain" (1996). Open Access Articles. 597.