Two functionally different protein isoforms are produced from the chicken estrogen receptor-alpha gene.
The existence of two forms of the chicken estrogen receptor-alpha protein (ER-alpha) in chicken tissues is demonstrated: the previously reported receptor (cER-alpha form I), which has a size of 66 kDa, and a new form (cER-alpha form II), which lacks the N-terminal 41 amino acids present in form I and thus gives rise to a protein of 61 kDa. Whereas the 66-kDa protein is the translation product of several cER-alpha mRNAs (A1-D), the cER-alpha protein isoform II is encoded by a new cER-alpha mRNA (A2), which is transcribed in vivo from a specific promoter that is located in the region of the previously assigned translation start site of the cER-alpha gene. SI nuclease mapping analysis reveals that cER-alpha mRNA A2 is liver enriched. The resulting cER-alpha forms I and II differ in their ability to modulate estrogen target gene expression in a promoter- and cell type-specific manner. Whereas cER-alpha form I activates or represses in a strictly E2-dependent manner, the truncated form is characterized by a partial transactivating or repressing activity in the absence of its ligand. Comparison of the N-terminal coding regions of different vertebrate ER-alpha reveal a conservation of the translation start methionine of the protein ER-alpha form II in other oviparous species but not in mammals. The expression of two classes of ER-alpha transcripts encoding the two ER-alpha receptor forms in the liver of Xenopus laevis and rainbow trout is demonstrated. Therefore, the existence of two functionally different protein isoforms produced from the ER-alpha gene is probably a common and specific feature in oviparous species.
Griffin
C
C
European Molecular Biology Laboratory, Heidelberg, Germany.
Flouriot
G
G
Sonntag-Buck
V
V
Gannon
F
F
D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002645:Chickens; D018387:Codon, Initiator; D017124:Conserved Sequence; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D047628:Estrogen Receptor alpha; D004967:Estrogens; D020033:Protein Isoforms; D012333:RNA, Messenger; D011960:Receptors, Estrogen