The oncogene jun and nuclear signalling.
The oncogene jun and nuclear signalling.
复制标题
癌基因jun和核信号传导。
DOI：
10.1016/0968-0004(89)90268-5
复制
发表时间：
1989
影响因子：
13.8
通讯作者：
Bos,TJ
中科院分区：
文献类型：
--
作者：
Vogt,PK;Bos,TJ
Jun是一种转录因子，也可以诱导致癌转化。它的功能等同。嵌合GCN 4 DNA结合结构域是从酵母到人保守的，并且与其天然DNA结合几种其他转录调节因子的衍生物具有同源性。Jun与fos蛋白通过被jun的结构域取代的结构域二聚化，可以形成称为亮氨酸拉链的α-螺旋结构域，并且jun-fos异二聚体结合以在酵母4中发挥GCN 4的功能。事实上，DNA和调节子转录的许多特定的非连锁基因，jun蛋白本身可以作为GCN 4转录激活因子在酵母中发挥作用，由转录癌症使用的去保守基序是癌基因jun。在过去的一年里，从酵母到人的氨基因子缺乏同源性，很明显，jun末端三分之二的分子细胞生长和细胞增殖的程序，是一个重要的细胞调控元件，它包含转录激活，通过与其他vator结构域特异性相互作用的短期启动。源自农杆菌表面蛋白和DNA的结构和信号，将细胞外的酵母tor或激素之间的功能同源性和短期信号转化为长期转录因子和癌基因，通过反应向细胞核传播。关于控制活跃在脊椎动物细胞中的激动人心的通道通过受体、转导转录和细胞生长的研究已经足够了，但是决定性的突破和转录因子蛋白质，以及细胞质会聚在这个基因上提供有关jun的性质的蛋白激酶。这些向心的，令人兴奋的新见解核sig-when发现，人类transshort-term信号引发长期钉，转录因子AP-1结合到相同的反应，产生改变pat-癌基因jun被发现作为共识序列作为酵母GCN 4基因表达的共同点。转录物-0.93 kb，细胞衍生的蛋白质遗传插入物（TGACTCA）。显然，如果功能调节蛋白发挥了中心作用，那么复制缺陷型AP-1和jun的基因组都与GCN 4在这一过程中的作用有关，结合传入逆转录病毒、禽肉瘤病毒17，它们可能彼此相关。和传出功能，以转换信号-（ASV 17），分离自自发的几条证据表明，这是通过改变鸡肉瘤1（图1）的细胞反应。ASV 17确实是6”7的情况。抗血清产生的转录水平的特定原因在鸡纤维肉瘤;它对两个肽的jun基因。几乎所有的细胞表面也能诱导致癌转化序列（一种来自胞质内的快速共质成分，在禽胚胎成纤维细胞中培养的DNA结合域中，短时间的信号链能诱导真。ASV的致癌潜力不同于发散性氨基致癌作用，如果定量改变或17是由于分子的jun基因末端区域的存在，则定性反应。直到最近，在ASV 17基因组中的转录-特异性地具有转录调节因子中的40 kDa蛋白质的jun尚未从ASV 17中序列切除，并且DNA亲和纯化的制剂显示具有致癌潜力，将其置于非转化性逆转录AP-1中。尽管有证据表明几种病毒载体与ASV 17型癌细菌结合，但在中表达的人jun克隆赋予了一种蛋白质，该蛋白质结合癌基因以控制对该载体的转基因性2。第一个以AP-1 DNA为共有序列。笔迹。第一个明确的例子表明，jun可能是更多的突变体的共识序列，以…
Jun is a transcription factor that can also induce oncogenic transformation. Its tional equivalence. A chimeric GCN4 DNA-binding domain is conserved from yeast to man and shows homology to derivative with its native DNA binding several other transcriptional regulators. Jun dimerizes with the fos protein through domain replaced by that of jun can an a-helical domain termed the leucine zipper, and the jun-fos heterodimers bind to function as GCN4 in yeast 4. In fact, the DNA and regulaw transcription of numerous specific unlinked genes, jun protein itself can function as GCN4 transcriptional activator in yeast, des-Conserved motifs used by transcription cancer is the oncogene jun. Over the pite the lack of homology in the aminofactors from yeast to man past year it has become evident thatjun terminal two-thirds of the molecules Programs of cell growth and differen-is an important cellular controlelement which contain the transcriptional actitiation are set in motion by short-term that interacts specifically with other vator domains 5. The structural and signals that originate with agrowth fac-proteins and with DNA, converting functional homology between a yeast tor or a hormone outside the cell and short-term signals into long-term transcription factor and an oncogene are propagated toward the nucleus by responses. Research on the control of active in vertebrate cells was exciting passage through receptors, transducer transcription and of cell growth has enough, but the decisive breakthrough and amplifierproteins, and cytoplasmic converged on this gene to provide concerning the nature of jun came protein kinases. These centripetal, exciting new insights into nuclear sig-when it was found that the human transhort-term signals elicit a long-term nailing, scription factor AP-1 binds to the same response that generates altered pat- The oncogene jun was discovered as consensus sequence as the yeast GCN4 terns of gene expression. Transcrip-a 0.93 kb, cell-derived genetic insert in protein (TGACTCA). Obviously, if tional regulatory proteins play a central the genome of the replication defective AP-1 and jun are both related to GCN4 role in this process, combining afferent retrovirus, avian sarcoma virus 17 they might be related to each other. and efferent functions to convert sig-(ASV 17), isolated from a spontaneous Several lines of evidence show that this nals into cellular responses by altering chicken sarcoma 1 (Fig. 1). ASV 17 is indeed the case 6" 7. Antisera generthe levels of transcription of specific causes fibrosarcomas in chickens; it ated against two peptides of the jun genes. Virtually all cell-surface and also induces oncogenic transformation sequence (one from within the concytoplasmic components of rapid, in avian embryonic fibroblasts in cul-served DNA-binding domain, the short-term signal chains can induce ture. The oncogenic potential of ASV other from the divergent aminooncogenesis if altered quantitatively or 17 is due to the presence of thejun gene terminal region of the molecule), react qualitatively. Until recently tran-in the ASV 17 genome-the jun specifically with a 40 kDa protein in scriptional regulators had not been sequence excised from ASV 17 and DNA affinity-purified preparations of shown to harbor oncogenic potential, placed into a non-transforming retro-AP-1. A humanjun clone expressed in although there is evidence tying several viral vector confers ASV 17-type onco-bacteria codes for a protein that binds oncogenes to the control of tran-genicity to that vector 2. The first to theAP-1 DNA consensus sequence. scription. The first definitive example indication that jun might be of more Mutants of the consensus sequence to of a …