Both the basic region and the 'leucine zipper' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation.
AUTOR(ES)
Dwarki, V J
RESUMO
Second messengers like cAMP can activate the transcription of genes containing consesus cAMP response element (CRE). A 43 kd nuclear phosphoprotein previously identified as the cAMP response element binding (CREB) protein has been shown to bind as a dimer to CRE and activate gene transcription. The rat and human CREB protein contain the 'leucine zipper' motif. We have analyzed the role of both leucine zipper domain and the amino-terminal basic region by making site-specific mutations. Our results show that the first three leucines int he leucine zipper domain are essential for efficient dimer formation. Mutations of two consecutive leucines in the leucine zipper domain completely abolish the ability to form dimers. Mutant CREB protein unable to form homodimers is also unable to bind to DNA. In contrast, however, mutations, in the DNA binding region had no effect on dimer formation but were unable to bind to CRE sites or activate transcription. We propose that CREB protein functions by forming homodimers which bind to CRE and activate transcription. Furthermore, the CREB protein needs to be phosphorylated before activating transcription. Finally, we show that the CREB basic region mutant acts as a trans-dominant transcriptional suppressor of wild-type CREB function.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=551651Documentos Relacionados
- The hepatitis B virus X protein targets the basic region-leucine zipper domain of CREB.
- A cyclic AMP-responsive element-binding transcriptional activator in Drosophila melanogaster, dCREB-A, is a member of the leucine zipper family.
- Differential Activation of the Transcription Factor Cyclic AMP Response Element Binding Protein (CREB) in Macrophages following Infection with Pathogenic and Nonpathogenic Mycobacteria and Role for CREB in Tumor Necrosis Factor Alpha Production
- Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes.
- Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain.