Expression and translation of the COX-1b gene in human cells--no evidence of generation of COX-1b protein.
Cyclooxygenase 1b (COX-1b) is a splice variant of COX-1, containing a retained intron 1 within the signal peptide sequence. COX-1b mRNA is found in many species, but the existence of a functionally active protein, which is possibly related to different species-dependent lengths of intron 1, is controversially discussed. The human intron 1 comprises 94 bp, and the resulting frameshift at the intron 1-exon 2 junction creates a premature stop codon. Nevertheless, full-length human COX-1b protein expression, including translated intron 1 and the signal peptide, has been reported and was explained by a frameshift repair. In this study, the fate of COX-1b mRNA in a human overexpression system is analyzed. Independent of the hypothetical frameshift repair mechanism, the splicing of the COX-1b intron 1, resulting in COX-1 mRNA and removal of the signal peptide during protein maturation, with subsequent generation of a COX-1 protein is demonstrated.
Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
Christina
C
Reinauer
Petra
P
Censarek
Gernot
G
Kaber
Artur-Aron
AA
Weber
Gerhard
G
Steger
Thorsten
T
Klamp
Karsten
K
Schrör
D000595:Amino Acid Sequence; D001483:Base Sequence; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D008099:Liver / Q000201:enzymology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013270:Stomach / Q000201:enzymology
D018076:DNA, Complementary; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3