The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A.
Many promoters respond transcriptionally to elevated levels of cAMP through the cAMP-responsive enhancer (CRE). Several proteins have been characterized which bind to the CRE and presumably modulate CRE-dependent transcription. Of these CRE-binding proteins, only CREB has been shown to be activated by cAMP-dependent protein kinase A (PKA), and as such, CREB represents the only basis for our understanding of cAMP-regulated transcriptional activity. In this report, we describe the complete cDNA sequence of another CRE-binding protein, ATF-1. This protein contains a consensus phosphorylation site for PKA and shares extensive homology with CREB in the region surrounding and carboxyl-terminal to the PKA site. ATF-1 does not contain sequences homologous to the glutamine-rich amino-terminal domain found in CREB, however. ATF-1, like CREB, is expressed in a wide variety of cell types, and ATF-1 is capable of dimerizing with CREB. Both ATF-1 homodimers and ATF-1/CREB heterodimers bind to the CRE but not to the related phorbol ester response element. ATF-1 is as active as CREB in its ability to mediate the transcriptional effects of PKA, and, because ATF-1 has a smaller effect on basal expression, it is actually more responsive than CREB to cAMP. These findings indicate that CREB is not unique in its ability to mediate cAMP-dependent transcriptional regulation.
Rehfuss
R P
RP
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Walton
K M
KM
Loriaux
M M
MM
Goodman
R H
RH
D051696:Activating Transcription Factors; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D051696:Activating Transcription Factors; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D011494:Protein Kinases