Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins

Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins
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N-myc:β-半乳糖苷酶融合蛋白的亚核定位和抗转化活性

DOI:
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发表时间:
1988
影响因子:
5.3
通讯作者:
H. Kondoh
H. Kondoh
中科院分区:
生物学2区
文献类型:
--
作者:
K. Ueno;K. Katoh;H. Kondoh

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N-myc 表达在哺乳动物发育中受到阶段和组织特异性调节,但其功能完全未知。我们寻找阻断 N-myc 活性的药物,以便从效果推断 N-myc 在明显复杂的过程中可能的功能。作为此类药物的候选者,我们测试了编码 N-myc:β-半乳糖苷酶融合蛋白的融合基因,以了解其对 N-myc 和活化的 H-ras 转染后大鼠胚胎原代成纤维细胞转化灶形成的影响。根据其对病灶形成的影响评估,其中一种基因构建体非常有效地拮抗 N-myc 活性,但没有明显影响细胞活力。该基因的产物不仅靶向细胞核,而且还积累在亚核基因座中,这些基因座可能代表正常 N-myc 蛋白所在的位点。低化学计量比下拮抗作用的发生表明融合蛋白基因以类似于显性失活突变的方式与N-myc基因竞争。
N-myc expression is under stage- and tissue-specific regulation in mammalian development, but its function is totally unknown. We sought agents to block N-myc activity in order to infer from the effect the possible function of N-myc in the apparently complex processes. As candidates for such agents, we tested fusion genes encoding N-myc:beta-galactosidase fusion proteins for their effects on the formation of transformed foci of rat embryo primary fibroblasts as the result of transfection with N-myc and activated H-ras. One of the gene constructs very efficiently antagonized N-myc activity, as assessed by its effect on focus formation, but did not appreciably affect cell viability. The product of this gene was not only targeted to the nucleus but also accumulated in subnuclear loci which may represent the sites where normal N-myc proteins reside. The occurrence of antagonistic effect at a low stoichiometric ratio suggested that the fusion protein gene competed with the N-myc gene in a fashion analogous to a dominant negative mutation.
myc 癌基因蛋白和小核核糖核蛋白颗粒的共定位。
DOI: 10.1101/sqb.1986.051.01.107
发表时间: 1986
期刊: Cold Spring Harbor symposia on quantitative biology
影响因子: --
作者:
Sullivan,NF;Watt,RA;Delannoy,MR;Green,CL;Spector,DL
通讯作者: Spector,DL
N-myc可以与ras协同转化培养中的正常细胞。
DOI: 10.1073/pnas.82.16.5455
发表时间: 1985
影响因子: 11.1
作者:
Yancopoulos,GD;Nisen,PD;Tesfaye,A;Kohl,NE;Goldfarb,MP;Alt,FW
通讯作者: Alt,FW
人类 N-myc 癌基因编码的蛋白质的鉴定和表征。
DOI: 10.1126/science.3008339
发表时间: 1986
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Slamon,DJ;Boone,TC;Seeger,RC;Keith,DE;Chazin,V;Lee,HC;Souza,LM
通讯作者: Souza,LM
新型多功能质粒载体,用于表达由与编码 β-半乳糖苷酶酶活性羧基末端部分的 lacZ 基因序列融合的克隆基因编码的杂合蛋白。
DOI: 10.1016/0378-1119(83)90169-5
发表时间: 1983
期刊: Gene
影响因子: 3.5
作者:
Shapira,SK;Chou,J;Richaud,FV;Casadaban,MJ
通讯作者: Casadaban,MJ