Molecular characterization of transcription factors that bind to the cAMP responsive region of the substance P precursor gene. cDNA cloning of a novel C/EBP-related factor.
A cAMP response element (CRE) plays an important role in the cAMP-mediated gene regulation. Several factors that recognize a CRE have been characterized, and it has been shown that they need either covalent modification by protein kinase A or a cofactor such as the adenovirus Ela to function as an activator. In this study we show that the substance P precursor gene expression is regulated by protein kinase A and identify the CRE sequence in its promoter region. We find that a novel factor and ATF2 bind to the region containing the CRE of the substance P precursor gene. The sequence analysis indicates that the novel protein, designated CELF, has a significant homology to C/EBP gene family proteins in the carboxyl-terminal part containing the basic region and the leucine zipper motif. Ubiquitous expression of CELF suggests that this factor is utilized by various genes. Cell-free transcription analyses indicate that CELF is a constitutive transcriptional activator without apparent phosphorylation by protein kinase A. These results demonstrate that multiple factors are responsible for transcriptional control of the substance P precursor gene through the CRE region.
Kageyama
R
R
Institute for Immunology, Kyoto University Faculty of Medicine, Japan.
Sasai
Y
Y
Nakanishi
S
S
D051698:Activating Transcription Factor 2; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D016350:Leucine Zippers / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D012313:RNA / Q000032:analysis; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013373:Substance P / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D022762:CCAAT-Enhancer-Binding Proteins; C497254:Cebpd protein, rat; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011498:Protein Precursors; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D013373:Substance P; D012313:RNA; D004247:DNA; D000242:Cyclic AMP; D011494:Protein Kinases