Castellazzi M, Loiseau L, Piu F, Sergeant A
Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure, UMR 49, CNRS, Lyon, France.
Oncogene. 1993 May;8(5):1149-60.
To investigate a possible role for c-Jun homodimers in c-Jun-mediated transformation, we designed two chimeric c-Jun derivatives, called c-Juneb1 and c-Jungcn4. In these chimeric derivatives the natural dimerization domain of c-Jun was replaced by the heterologous homodimerization domain of the Epstein-Barr virus EB1 or the yeast GCN4 transcription factor. Chick embryo fibroblasts chronically infected with retroviruses expressing c-Jun, c-Juneb1 or c-Jungcn4 are transformed. Infection with each construction results in sustained growth in low serum and development of colonies from single cells in agar with similar efficiencies. In contrast to c-Jun, c-Juneb1 and c-Jungcn4 confer additional phenotypic alterations related to in vitro transformation including a condensed cell morphology and ability to develop highly invasive, fast growing colonies in agar. These data suggest that c-Jun homodimers can transform chick embryo fibroblasts and activate cellular functions which influence cell morphology and invasive potential in agar. These findings are consistent with the notion that cellular transformation by c-jun is mediated by c-Jun homodimers.
为了研究c-Jun同二聚体在c-Jun介导的细胞转化中的可能作用，我们设计了两种嵌合c-Jun衍生物，分别称为c-Juneb1和c-Jungcn4。在这些嵌合衍生物中，c-Jun的天然二聚化结构域被爱泼斯坦-巴尔病毒EB1或酵母GCN4转录因子的异源同二聚化结构域所取代。长期感染表达c-Jun、c-Juneb1或c-Jungcn4的逆转录病毒的鸡胚成纤维细胞会发生转化。用每种构建体感染都会导致在低血清中持续生长，并在琼脂中从单细胞形成集落，效率相似。与c-Jun不同，c-Juneb1和c-Jungcn4会带来与体外转化相关的额外表型改变，包括浓缩的细胞形态以及在琼脂中形成高度侵袭性、快速生长集落的能力。这些数据表明，c-Jun同二聚体可以转化鸡胚成纤维细胞并激活影响细胞形态和在琼脂中侵袭潜能的细胞功能。这些发现与c-jun介导的细胞转化是由c-Jun同二聚体介导的观点一致。
