Gertler F B, Chiu C Y, Richter-Mann L, Chin D J
Department of Pharmacology, University of California, San Francisco 94143.
Mol Cell Biol. 1988 Jul;8(7):2713-21. doi: 10.1128/mcb.8.7.2713-2721.1988.
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in Drosophila melanogaster synthesizes mevalonate for the production of nonsterol isoprenoids, which are essential for growth and differentiation. To understand the regulation and developmental role of HMG CoA reductase, we cloned the D. melanogaster HMG CoA reductase gene. The nucleotide sequence of the Drosophila HMG CoA reductase was determined from genomic and cDNA clones. A 2,748-base-pair open reading frame encoded a polypeptide of 916 amino acids (Mr, 98,165) that was similar to the hamster HMG CoA reductase. The C-terminal region had 56% identical residues and the N-terminal region had 7 potential transmembrane domains with 32 to 60% identical residues. In hamster HMG CoA reductase, the membrane regions were essential for posttranslational regulation. Since the Drosophila enzyme is not regulated by sterols, the strong N-terminal similarity was surprising. Two HMG CoA reductase mRNA transcripts, approximately 3.2 and 4 kilobases, were differentially expressed throughout Drosophila development. Mevalonate-fed Schneider cells showed a parallel reduction of both enzyme activity and abundance of the 4-kilobase mRNA transcript.
果蝇中的3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶合成甲羟戊酸用于生产非甾醇类异戊二烯，这对生长和分化至关重要。为了解HMG CoA还原酶的调控及发育作用，我们克隆了果蝇的HMG CoA还原酶基因。果蝇HMG CoA还原酶的核苷酸序列是从基因组和cDNA克隆中确定的。一个2748个碱基对的开放阅读框编码了一个916个氨基酸的多肽（Mr，98165），它与仓鼠HMG CoA还原酶相似。C末端区域有56%的相同残基，N末端区域有7个潜在的跨膜结构域，相同残基为32%至60%。在仓鼠HMG CoA还原酶中，膜区域对翻译后调控至关重要。由于果蝇酶不受固醇调节，N末端的高度相似性令人惊讶。两种HMG CoA还原酶mRNA转录本，约3.2和4千碱基，在果蝇发育过程中差异表达。用甲羟戊酸喂养的施奈德细胞显示出酶活性和4千碱基mRNA转录本丰度的平行降低。
