Nucleotide sequence and estrogen induction of Xenopus laevis 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
We have isolated and sequenced overlapping cDNA clones encompassing the entire protein coding region of Xenopus laevis 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). This 3-kilobase cDNA codes for an 883-amino acid protein, which exhibits extensive amino acid sequence homology to mammalian HMG-CoA reductases. The highly conserved 341-amino acid membrane spanning domain exhibits 89% amino acid sequence identity with hamster HMG-CoA reductase. In contrast to the high degree of homology in the coding regions of the mRNAs, the nucleotide sequences of the 5'- and 3'-untranslated regions of Xenopus and mammalian HMG-CoA reductase mRNAs exhibit negligible homology. Primer extension data suggests that Xenopus HMG-CoA reductase mRNA is transcribed from multiple initiation sites. The Xenopus HMG-CoA reductase cDNA clones were used as hybridization probes to examine estrogen regulation of hepatic HMG-CoA reductase mRNA levels. Northern blot analysis demonstrates that estradiol-17 beta induced HMG-CoA reductase mRNA in livers of male X. laevis 10-fold within 24 h. Reductase mRNA levels reach a plateau 23-fold higher than basal levels between 5 and 8 days after initial estrogen administration. In contrast to the vitellogenin and retinol binding protein genes whose transcription is induced by estrogen in Xenopus liver, the runoff transcription rate of HMG-CoA reductase does not increase significantly on administration of estradiol-17 beta. These data suggest that the estrogen induction of HMG-CoA reductase mRNA may be achieved through posttranscriptional mechanisms.
Chen
H J
HJ
Department of Biochemistry, University of Illinois, Urbana 61801.
Shapiro
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014982:Xenopus laevis / Q000235:genetics*
D015342:DNA Probes; D012333:RNA, Messenger; D004958:Estradiol; D006903:Hydroxymethylglutaryl CoA Reductases