Artificial oncoproteins: modified versions of the yeast bZip protein GCN4 induce cellular transformation

Makoto Nishizawa; Shu-Ling Fu; Kohsuke Kataoka; Peter K Vogt

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Artificial oncoproteins: modified versions of the yeast bZip protein GCN4 induce cellular transformation

机译：人造野生蛋白：酵母Bzip蛋白GCN4的改性版本诱导细胞转化

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We have constructed artificial AP-1 proteins containing elements derived from yeast GCN4 and from the herpes simplex virus activator VP16. These proteins can only homodimerize but do not heterodimerize, and lacking significant homology to Jun outside the DNA-binding domain, they are largely unaffected by proteins that modulate Jun. Constructs in which the transactivation domain of GCN4 is replaced by that of VP16 induce oncogenic transformation in cultures of chicken embryo fibroblasts. The availability of transforming VP16-GCN4 fusion proteins permits an evaluation of downstream target genes, based on the hypothesis that transformation-relevant targets should be common between Jun and the artificial AP-1 proteins. In a pilot study, we examined the expression of several Jun target genes in cells transformed by the VP16-GCN4 fusions and found that some of the Jun targets are not upregulated by the GCN4-derived transforming construct, suggesting that their upregulation in Jun-transformed cells is not essential for cell transformation. We have further constructed a regulatable GCN4-VP16 protein that will permit a kinetic characterization of target gene responses and will facilitate discrimination between direct and indirect targets.

机译：我们构建了含有衍生自酵母GCN4的元素和疱疹病毒活化剂VP16的人工AP-1蛋白。这些蛋白质只能同态化，但不具有杂于二聚体，并且缺乏对DNA结合结构域之外的显着同性恋，它们主要不受调节Jun的蛋白质的影响。其中GCN4的转移结构域由VP16诱导致癌转化的构建体在鸡胚成纤维细胞的培养中。转化VP16-GCN4融合蛋白的可用性允许评估下游靶基因，基于转化相关靶标在Jun和人工AP-1蛋白之间应该是常见的假设。在试验研究中，我们研究了VP16-GCN4融合转化的细胞中几个Jun靶基因的表达，发现一些Jun靶不会通过GCN4衍生的转化构建体上调，表明它们在jun转换的上调细胞不是细胞转化必不可少的。我们进一步构建了一种可调节的GCN4-VP16蛋白，允许靶基因反应的动力学表征，并将促进直接和间接目标之间的歧视。

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《Oncogene》 |2003年第39期|共11页
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Makoto Nishizawa; Shu-Ling Fu; Kohsuke Kataoka; Peter K Vogt;
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1. A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt [J] . Masahiro Aoki, Erik Blazek, Peter K. Vogt Proceedings of the National Academy of Sciences of the United States of America . 2001,第1期

机译：激酶mTOR在癌蛋白P3k和Akt诱导的细胞转化中的作用
2. Replacement of invariant bzip residuces within the basic region of the yeast transcriptional activator GCN4 can Change its DNA binding specificity [J] . Benno Müller-Hill, Brigitte Kisters-Woike, Brigitte von Wilcken-Bergmann, Nucleic acids research . 1994,第21期

机译：酵母转录激活因子GCN4基本区域内不变bzip残基的替换可改变其DNA结合特异性
3. Highly conserved residues in the bZIP domain of yeast GCN4 are not essential for DNA binding. [J] . W T Pu, K Struhl Molecular and Cellular Biology . 1991,第10期

机译：酵母GCN4的bZIP结构域中高度保守的残基对于DNA结合不是必需的。
4. Convergent molecular modeling of alpha-helix-and beta-sheet-inducers towards artificial transcription factors of the GCN4 and Met-repressor classes [C] . Christian Lehmann European Peptide Symposium . 2002

机译：α-螺旋和β-型诱导符到GCN4和Met-ext压缩课程人工转录因子的收敛分子建模
5. Heat shock transcription factor 1 and heat shock protein 72 play a critical role in HER2-induced cellular transformation and tumorigenesis [D] . Meng, Le 2012

机译：热休克转录因子1和热休克蛋白72在HER2诱导的细胞转化和肿瘤发生中起关键作用
6. A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt [O] . Masahiro Aoki, Erik Blazek, Peter K. Vogt 2001

机译：激酶mTOR在诱导的细胞转化中的作用。癌蛋白P3k和Akt
7. Artificial oncoproteins: modified versions of the yeast bZip protein GCN4 induce cellular transformation [O] . Makoto Nishizawa, Shu-Ling Fu, Kohsuke Kataoka, 2003

机译：人造野生蛋白：酵母Bzip蛋白GCN4的改性版本诱导细胞转化

Artificial oncoproteins: modified versions of the yeast bZip protein GCN4 induce cellular transformation

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