The bovine papillomavirus E2 transactivator is stimulated by the E1 initiator through the E2 activation domain.
Bovine papillomavirus type 1 (BPV-1) encodes two regulatory proteins, E1 and E2, that are essential for viral replication and transcription. E1, an ATP-dependent helicase, binds to the viral ori and is essential for viral replication, while the viral transcriptional activator, E2, plays cis-dominant roles in both viral replication and transcription. At low reporter concentrations, E1 stimulates E2 enhancer function, while at high reporter concentrations, repression results. An analysis of cis requirements revealed that neither replication nor specific E1-binding sites are required for the initiators' effect on E2 transactivator function. Though no dependence on E1-binding sites was found, analysis of E1 DNA binding and ATPase mutants revealed that both domains are required for E1 modulation of E2. Through the use of E2 fusion-gene constructs we showed that a heterologous DNA-binding domain could be substituted for the E2 DNA-binding domain and this recombinant protein remained responsive to E1. Furthermore, E1 could rescue activation domain mutants of E2 defective for transactivation. These data suggest that E1 stimulation of E2 involves interactions between E1 and the E2 activation domain on DNA. We speculate that E1 may allosterically interact with the E2 activation domain, perhaps stabilizing a particular structure, which increases the enhancer function of E2.
Parker
L M
LM
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.
Harris
S
S
Gossen
M
M
Botchan
M R
MR
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D002417:Cattle; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D009154:Mutation; D015534:Trans-Activators; D014760:Viral Fusion Proteins / Q000235:genetics; D014764:Viral Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; C051550:E2 protein, Bovine papillomavirus; D015534:Trans-Activators; D014760:Viral Fusion Proteins; D014764:Viral Proteins