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病毒erbA癌基因蛋白在动物细胞中是一种组成型阻遏物,而在酵母中则是一种激素调节的激活物。

The viral erbA oncogene protein, a constitutive repressor in animal cells, is a hormone-regulated activator in yeast.

作者信息

Privalsky M L, Sharif M, Yamamoto K R

机构信息

Department of Microbiology, University of California, Davis 95616.

出版信息

Cell. 1990 Dec 21;63(6):1277-86. doi: 10.1016/0092-8674(90)90423-c.

DOI:10.1016/0092-8674(90)90423-c
PMID:1979758
Abstract

The v-erbA oncogene is a retrovirus-transduced and altered copy of a cellular gene for a thyroid hormone receptor. In animal cells, the v-erbA protein fails to respond to hormone and acts as a dominant negative allele, inhibiting gene activation normally conferred by the wild-type thyroid hormone receptor. We report here that, unexpectedly, the v-erbA protein acts as a hormone-regulated transcriptional activator in S. cerevisiae. We suggest that the ability of v-erbA protein to function as a transcriptional repressor or an activator is determined by interaction with, or modification by, other cellular factors, and that this phenomenon may be relevant to understanding ligand regulation of the normal thyroid and steroid hormone receptors.

摘要

v-erbA癌基因是一种逆转录病毒转导并改变的细胞甲状腺激素受体基因拷贝。在动物细胞中,v-erbA蛋白对激素无反应,并作为显性负等位基因发挥作用,抑制野生型甲状腺激素受体通常赋予的基因激活。我们在此报告,出乎意料的是,v-erbA蛋白在酿酒酵母中作为激素调节的转录激活因子发挥作用。我们认为,v-erbA蛋白作为转录抑制因子或激活因子发挥功能的能力是由与其他细胞因子的相互作用或修饰所决定的,并且这种现象可能与理解正常甲状腺和类固醇激素受体的配体调节有关。

相似文献

1
The viral erbA oncogene protein, a constitutive repressor in animal cells, is a hormone-regulated activator in yeast.病毒erbA癌基因蛋白在动物细胞中是一种组成型阻遏物,而在酵母中则是一种激素调节的激活物。
Cell. 1990 Dec 21;63(6):1277-86. doi: 10.1016/0092-8674(90)90423-c.
2
Functional domains of the v-erbA protein necessary for oncogenesis are required for transcriptional activation in Saccharomyces cerevisiae.致癌作用所需的v-erbA蛋白功能域对于酿酒酵母中的转录激活是必需的。
Oncogene. 1993 Jun;8(6):1465-75.
3
Identification of a domain required for oncogenic activity and transcriptional suppression by v-erbA and thyroid-hormone receptor alpha.鉴定v-erbA和甲状腺激素受体α致癌活性及转录抑制所需的结构域。
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10668-72. doi: 10.1073/pnas.90.22.10668.
4
A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor).在v-ErbA中缺失的保守C末端序列对c-ErbA(甲状腺激素受体)的生物学活性至关重要。
Mol Cell Biol. 1993 Jun;13(6):3675-85. doi: 10.1128/mcb.13.6.3675-3685.1993.
5
Kindred S thyroid hormone receptor is an active and constitutive silencer and a repressor for thyroid hormone and retinoic acid responses.亲属S甲状腺激素受体是一种活性和组成型沉默子,也是甲状腺激素和视黄酸反应的阻遏物。
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10633-7. doi: 10.1073/pnas.89.22.10633.
6
V-erbA requires auxiliary proteins for dominant negative activity.V-erbA发挥显性负性活性需要辅助蛋白。
Oncogene. 1993 Jan;8(1):55-65.
7
Rat liver c-erb A beta 1 thyroid hormone receptor is a constitutive activator in yeast (Saccharomyces cerevisiae): essential role of domains D,E and F in hormone-independent transcription.大鼠肝脏c-erb Aβ1甲状腺激素受体在酵母(酿酒酵母)中是一种组成型激活剂:结构域D、E和F在非激素依赖性转录中的重要作用。
Biochem Biophys Res Commun. 1991 Aug 15;178(3):1167-75. doi: 10.1016/0006-291x(91)91015-5.
8
V-erbA and c-erbA proteins enhance transcriptional activation by c-jun.
Oncogene. 1992 May;7(5):953-60.
9
The lack of transcriptional activation of the v-erbA oncogene is in part due to a mutation present in the DNA binding domain of the protein.v-erbA癌基因转录激活的缺失部分归因于该蛋白质DNA结合结构域中存在的一种突变。
Nucleic Acids Res. 1990 Aug 11;18(15):4489-97. doi: 10.1093/nar/18.15.4489.
10
Thyroid hormone receptor/and v-erbA. A single amino acid difference in the C-terminal region influences dominant negative activity and receptor dimer formation.
J Biol Chem. 1991 Jun 25;266(18):11589-93.

引用本文的文献

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Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties.维甲酸受体和甲状腺激素受体的异二聚体表现出独特的组合调控特性。
Mol Endocrinol. 2005 Apr;19(4):863-78. doi: 10.1210/me.2004-0210. Epub 2005 Jan 13.
2
Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of Hsp90-dependent signaling proteins.p23和安莎霉素类抗生素在Hsp90依赖性信号蛋白功能中的遗传与生化分析。
Mol Cell Biol. 1998 Jun;18(6):3330-9. doi: 10.1128/MCB.18.6.3330.
3
Conserved interaction of the papillomavirus E2 transcriptional activator proteins with human and yeast TFIIB proteins.
乳头瘤病毒E2转录激活蛋白与人及酵母TFIIB蛋白的保守相互作用。
J Virol. 1997 Oct;71(10):8041-7. doi: 10.1128/JVI.71.10.8041-8047.1997.
4
RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.RAC3,一种与类固醇/核受体相关的共激活因子,与SRC-1和TIF2相关。
Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8479-84. doi: 10.1073/pnas.94.16.8479.
5
Thyroid hormone resistance syndrome manifests as an aberrant interaction between mutant T3 receptors and transcriptional corepressors.甲状腺激素抵抗综合征表现为突变型T3受体与转录共抑制因子之间的异常相互作用。
Mol Endocrinol. 1997 Apr;11(4):470-80. doi: 10.1210/mend.11.4.9914.
6
Cross-talk between thyroid hormone and specific retinoid X receptor subtypes in yeast selectively regulates cognate ligand actions.甲状腺激素与酵母中特定视黄酸X受体亚型之间的相互作用选择性地调节同源配体的作用。
Gene Expr. 1996;6(3):169-84.
7
Human nuclear receptor heterodimers: opportunities for detecting targets of transcriptional regulation using yeast.人类核受体异二聚体:利用酵母检测转录调控靶点的机遇。
Gene Expr. 1996;5(4-5):255-68.
8
Activation and repression by nuclear hormone receptors: hormone modulates an equilibrium between active and repressive states.核激素受体的激活与抑制:激素调节活性状态与抑制状态之间的平衡。
Mol Cell Biol. 1996 Jul;16(7):3807-13. doi: 10.1128/MCB.16.7.3807.
9
A role for Hsp90 in retinoid receptor signal transduction.热休克蛋白90在视黄酸受体信号转导中的作用。
Mol Biol Cell. 1995 Dec;6(12):1833-42. doi: 10.1091/mbc.6.12.1833.
10
Reconstitution of retinoid X receptor function and combinatorial regulation of other nuclear hormone receptors in the yeast Saccharomyces cerevisiae.酿酒酵母中视黄酸X受体功能的重建及其他核激素受体的组合调控。
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6929-33. doi: 10.1073/pnas.90.15.6929.