Abstract
cAMP regulates the expression of a number of genes through the protein kinase A-mediated phosphorylation of CREB at Ser-133. The effects of Ser-133 phosphorylation appear to be primarily transmitted through a modulatory kinase-inducible domain in CREB that functions cooperatively with a 120-amino acid glutamine-rich region (Q2) to stimulate transcription. Indeed, the kinase-inducible domain activity alone is not sufficient to sustain a transcriptional response as illustrated by the CREM family of repressors, which contain the kinase-inducible domain but lack the Q2 region. Here we demonstrate that Q2 functions as a potent constitutive activator in vitro. The transcription factor TFIID fraction supports transcriptional activation by Q2, although the "TATA" binding protein alone does not, suggesting that other components of the TFIID complex mediate the response to CREB Q2. In fact, Q2 associates with the TATA binding protein-associated factor dTAFII110. As the transcriptionally inactive CREM alpha and beta proteins lack sequences in Q2 that are necessary for binding dTAFII110, our results suggest that these proteins may repress transcription because they are unable to interact with the basal transcription complex.
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