Two classes of mutant mammary tumor virus-infected HTC cell with defects in glucocorticoid-regulated gene expression.
Two classes of mutant mammary tumor virus-infected HTC cell with defects in glucocorticoid-regulated gene expression.
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两类突变乳腺肿瘤病毒感染的 HTC 细胞在糖皮质激素调节的基因表达方面存在缺陷。
DOI：
10.1128/mcb.3.2.149-160.1983
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发表时间：
1983
影响因子：
5.3
通讯作者：
Yamamoto,KR
中科院分区：
文献类型：
--
作者：
Firestone,GL;Yamamoto,KR
我们分离了M1.54（一种乳腺肿瘤病毒[MTV]感染的大鼠肝癌[HTC]细胞系，含有多种整合的原病毒）的突变衍生物，其不能表达激素诱导的细胞表面病毒糖蛋白。在野生型M1.54中，合成的糖皮质激素地塞米松选择性地刺激MTV RNA的合成速率。此外，地塞米松对由MTV糖基化前体多蛋白加工的四种细胞表面病毒糖蛋白中的三种的翻译后成熟至关重要；第四种成熟种是组成性地产生的。描述了两种突变表型；每一种都含有糖皮质激素受体，在激素亲和力、细胞内浓度、核易位效率、dna -纤维素层析和沉降速率方面与野生型受体难以区分。在一类突变系CR1中，地塞米松不能刺激MTV基因的低基础转录率；令人惊讶的是，激素对酪氨酸转氨酶活性的调节在CR1中也有缺陷，而其他几种对地塞米松的细胞反应是正常的。在以CR4为代表的第二类突变体中，地塞米松刺激MTV转录本的合成，与M1.54中产生的转录本没有区别，但只表达构成细胞表面的病毒糖蛋白。因此，这些突变体定义了糖皮质激素在HTC细胞中调节基因表达的两个不同且新颖的方面：CR4在激素诱导的蛋白质成熟途径中存在缺陷，该途径作用于特定的病毒（可能是细胞）前体多肽，而CR1的病变似乎影响了M1.54中通常由糖皮质激素控制的基因产物子集的表达。
We have isolated mutant derivatives of M1.54 (a mammary tumor virus [MTV]-infected rat hepatoma [HTC] cell line containing multiple integrated proviruses) that fail to express hormone-inducible cell surface viral glycoproteins. In wild-type M1.54, the synthetic glucocorticoid dexamethasone selectively stimulates the rate of synthesis of MTV RNA. In addition, dexamethasone is essential for posttranslational maturation of three of the four cell surface viral glycoproteins processed from the MTV glycosylated precursor polyprotein; the fourth mature species is produced constitutively. Two mutant phenotypes are described; each contains glucocorticoid receptors that are indistinguishable from the wild-type receptor with respect to hormone affinity, intracellular concentration, nuclear translocation efficiency, DNA-cellulose chromatography, and sedimentation rate. In one class, represented by the mutant line CR1, dexamethasone fails to stimulate the low basal rate of MTV gene transcription; surprisingly, hormonal regulation of tyrosine aminotransferase activity is also defective in CR1, whereas several other cellular responses to dexamethasone are normal. In the second class of mutants, represented by CR4, dexamethasone stimulates synthesis of MTV transcripts indistinguishable from those produced in M1.54, but only the constitutive cell surface viral glycoprotein is expressed. Thus, these mutants define two distinct and novel aspects of glucocorticoid regulated gene expression in HTC cells: CR4 contains a defect in a hormone inducible protein maturation pathway that acts on specific viral (and presumably cellular) precursor polypeptides, whereas the lesion in CR1 appears to affect the expression of a subset of the gene products normally under glucocorticoid control in M1.54.