A novel cyclic AMP response element-binding protein-1 (CREB-1) splice product may down-regulate CREB-1 activity.
In this report we identify novel spliced forms of cyclic AMP (cAMP) response element-binding protein-1 (CREB-1) mRNA. These forms contained an additional 17 nucleotide insert, which we refer to as the beta exon, located between exons 4 and 7 of the delta, and 5 and 7 of the alpha forms of CREB-1 transcript (nomenclature of Ruppert et al. 1992; EMBO Journal 11, 1503-1512). The inclusion of the beta exon led to the generation of mRNAs in which the frame of CREB-1 sequences 3' to the exon was shifted such that the encoded proteins terminate after the transactivation domain, but before the target serine for cAMP-dependent protein kinase. The beta exon-containing CREB-1 mRNAs were more abundant in tissues that respond poorly to cAMP, suggesting that the generation of beta CREB-1 mRNAs may contribute to the down-regulation of CREB-1 activity and cAMP responsiveness.
Ellis
M J
MJ
Gene Expression Laboratory, Imperial Cancer Research Fund, London, UK.
Hurst
H C
HC
Goodbourn
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002822:Choriocarcinoma / Q000235:genetics / Q000473:pathology; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000145:classification / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006367:HeLa Cells / Q000737:chemistry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010920:Placenta / Q000737:chemistry; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000242:Cyclic AMP