Structure of the human cyclo-oxygenase-2 gene.
Cyclo-oxygenase (Cox), a rate-limiting enzyme in the synthesis of prostanoids, is encoded by two genes, Cox-1 and Cox-2, which are differentially expressed and regulated. Human Cox-1 and -2 polypeptides share 61% primary sequence identity. While the expression of Cox-1 is maximal in quiescent cells. Cox-2 expression is induced by growth factors and cytokines. We have screened a human genomic library with a probe from the 5'-untranslated region (UTR) of the human Cox-2 (hCox-2) cDNA and isolated two overlapping genomic clones. We have determined the DNA sequence of 0.8 kb upstream of the transcription start site, 6 kb of protein coding region, which includes 10 exons and 9 introns, as well as 2.5 kb of the 3'-UTR. The structures of the hCox-1 and hCox-2 and the murine TIS10 (Cox-2) genes are highly conserved, with a few exceptions. The 3'-UTRs of the Cox-1 and -2 genes are distinct; for example, the largest exon in the Cox-2 gene encodes the entire 3'-UTR, containing 22 copies of the 'AUUUA' RNA instability element. Sequence analysis of the 5'-flanking region has shown several potential transcription regulatory sequences, including a TATA box, a C/EBP motif, two AP-2 sites, three SP1 sites, two NF-kappa B sites, a CRE motif and an Ets-1 site. These efforts serve as a basis for future studies on transcriptional and post-transcriptional mechanisms of Cox-2 gene regulation.
Appleby
S B
SB
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, MD 20855.
Ristimäki
A
A
Neilson
K
K
Narko
K
K
Hla
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015698:Genomic Library; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000235:genetics*; D015183:Restriction Mapping; D014158:Transcription, Genetic / Q000235:genetics
D018076:DNA, Complementary; D011451:Prostaglandin-Endoperoxide Synthases