Chimeras of herpes simplex viral VP16 and jun are oncogenic.
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.
Schuur
E R
ER
Department of Microbiology, University of Southern California School of Medicine, Los Angeles.
Parker
E J
EJ
Vogt
P K
PK
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics*; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D018139:Simplexvirus; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D016759:Oncogene Protein p65(gag-jun); D011993:Recombinant Fusion Proteins