Further characterization of a somatic cell mutant defective in regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
Further characterization of a somatic cell mutant defective in regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
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3-羟基-3-甲基戊二酰辅酶 A 还原酶调节缺陷的体细胞突变体的进一步表征。
DOI：
10.1007/bf01535308
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Sinensky,M
中科院分区：
文献类型：
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作者：
Peffley,D;Miyake,J;Leonard,S;vonGunten,C;Sinensky,M
哺乳动物细胞合成甲戊酸的两种酶，3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)合成酶和HMG-CoA还原酶，被证明受外源类固醇的调节。已经证明，这些enyme至少部分地受到它们合成的转录控制的调控。我们之前已经描述了CHO-K1细胞系的一个体细胞突变(CR1)，它在调节这些酶的活性方面存在缺陷，对外源类固醇的反应存在缺陷。在这份报告中，我们证明了该突变体对HMG-CoA还原酶和HMG-CoA合成酶的mRNA水平的调节是有缺陷的。在HMG-CoA还原酶的情况下，这种明显的转录控制的丧失并不伴随着该酶合成调控的类似丧失。这一观察结果与先前的研究一致，表明HMG-CoA还原酶可以被翻译调控。我们还发现CR1细胞表现出结构性的快速降解HMG-CoA还原酶的速度。
Two enzymes of mammalian cellular mevalonate biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, have been shown to be regulated by exogenous sterols. It has been demonstrated that these enymes are regulated, at least in part, by transcriptional control of their synthesis. We have previously described a somatic cell mutant (CR1) of the CHO-K1 cell line that is defective in regulation of the activity of these enzymes in response to exogenous sterols. In this report, we demonstrate that this mutant is defective in regulation of the mRNA levels for HMG-CoA reductase and HMG-CoA synthase by 25-hydroxycholesterol and mevinolin. In the case of HMG-CoA reductase, this loss of apparent transcriptional control is not accompanied by a comparable loss in regulation of synthesis of this enzyme. This observation is consistent with prior studies suggesting that HMG-CoA reductase can be regulated translationally. We also show that CR1 cells exhibit a constitutively rapid rate of degradation of HMG-CoA reductase.