CHIMERAS OF HERPES-SIMPLEX VIRAL VP16 AND JUN ARE ONCOGENIC

The Jun protein binds DNA and regulates transcription as a component o f the AP-1 transcription factor complex. In its oncogenic form, Jun ca n transform cells in culture and cause tumors in animals. Both trans-a ctivation 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 wer e explored by replacing the trans-activation domains of c-Jun and its oncogenic counterpart, v-Jun, with the constitutively active trans-act ivation 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 tha n c-Jun. Substitutions of a phenylalanine in the VP16 domain of the VP 16-c-Jun chimera diminished or abolished transformation. Each of the c himeras bound to the AP-1 consensus recognition sequence from the coll agenase promoter or from the human T-cell leukemia virus type I long t erminal repeat in vitro. None of the VP16-Jun chimeras efficiently sti mulated transcription from the collagenase promoter or an artificial p romoter containing the human T-cell leukemia virus type I element in v ivo. These results demonstrate that the Jun trans-activation domain ca n be replaced by a heterologous trans-activation domain with retention of oncogenic activity. However, this oncogenic activity is not reflec ted in the trans-activating properties of the chimeras.