Schuur E R, Parker E J, Vogt P K
Department of Microbiology, University of Southern California School of Medicine, Los Angeles.
Cell Growth Differ. 1993 Sep;4(9):761-8.
The Jun protein binds DNA and regulates transcription as a component of the AP-1 transcription factor complex. In its oncogenic form, Jun can transform cells in culture and cause tumors in animals. Both trans-activation and transformation require several functional domains of Jun, including an amino-terminal trans-activation domain. In this study, properties of Jun required for trans-activation and transformation were explored by replacing the trans-activation domains of c-Jun and its oncogenic counterpart, v-Jun, with the constitutively active trans-activation domain from the herpes simplex virus VP16 protein. The VP16-v-Jun chimera retained similar oncogenic properties to its parent, v-Jun. The VP16-c-Jun chimera, however, was considerably more oncogenic than c-Jun. Substitutions of a phenylalanine in the VP16 domain of the VP16-c-Jun chimera diminished or abolished transformation. Each of the chimeras bound to the AP-1 consensus recognition sequence from the collagenase promoter or from the human T-cell leukemia virus type I long terminal repeat in vitro. None of the VP16-Jun chimeras efficiently stimulated transcription from the collagenase promoter or an artificial promoter containing the human T-cell leukemia virus type I element in vivo. These results demonstrate that the Jun trans-activation domain can be replaced by a heterologous trans-activation domain with retention of oncogenic activity. However, this oncogenic activity is not reflected in the trans-activating properties of the chimeras.
Jun蛋白作为AP-1转录因子复合物的一个组成部分，可结合DNA并调节转录。在其致癌形式中，Jun可在培养物中转化细胞并在动物体内引发肿瘤。反式激活和转化都需要Jun的几个功能结构域，包括一个氨基末端反式激活结构域。在本研究中，通过用单纯疱疹病毒VP16蛋白的组成型活性反式激活结构域替换c-Jun及其致癌对应物v-Jun的反式激活结构域，探索了反式激活和转化所需的Jun的特性。VP16-v-Jun嵌合体保留了与其亲本v-Jun相似的致癌特性。然而，VP16-c-Jun嵌合体比c-Jun的致癌性要强得多。在VP16-c-Jun嵌合体的VP16结构域中用苯丙氨酸替代会减弱或消除转化作用。每个嵌合体在体外均与来自胶原酶启动子或人I型T细胞白血病病毒长末端重复序列的AP-1共有识别序列结合。在体内，没有一个VP16-Jun嵌合体能够有效地刺激来自胶原酶启动子或含有I型人T细胞白血病病毒元件的人工启动子的转录。这些结果表明，Jun反式激活结构域可以被异源反式激活结构域取代，并保留致癌活性。然而，这种致癌活性并未体现在嵌合体的反式激活特性中。
