Characterization of a bipartite activator domain in transcription factor CREB.
In this paper, we characterize a trans-activating region in CREB, termed alpha, that interacts cooperatively with the kinase A phosphorylation motif to stimulate transcription. The alpha region appears to be encoded by an alternate exon that is deleted in a CREB-related cDNA named delta CREB. Both proteins are expressed in eukaryotic cells, although the activity of CREB is 10-fold higher than that of delta CREB. Circular dichroism data on a synthetic "alpha peptide" combined with results from in vitro mutagenesis experiments support the hypothesis that the alpha region contains an amphipathic alpha helix whose structure is critical to CREB activity. We propose that phosphorylation by kinase A may stimulate CREB activity in part by modulating the structure of alpha and thus may stimulate its ability to interact with other proteins in the polymerase II complex.
Yamamoto
K K
KK
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Gonzalez
G A
GA
Menzel
P
P
Rivier
J
J
Montminy
M R
MR
D000310:Adrenal Gland Neoplasms; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010673:Pheochromocytoma; D010957:Plasmids; D011487:Protein Conformation; D051381:Rats; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA