Lm. Parker et al., The bovine papillomavirus E2 transactivator is stimulated by the E1 initiator through the E2 activation domain, VIROLOGY, 270(2), 2000, pp. 430-443
Bovine papillomavirus type 1 (BPV-1) encodes two regulatory proteins, E1 an
d E2, that are essential for viral replication and transcription. E1, an AT
P-dependent helicase, binds to the viral ori and is essential for viral rep
lication, while the viral transcriptional activator, E2, plays cis-dominant
roles in both viral replication and transcription. At low reporter concent
rations, E1 stimulates E2 enhancer function, while at high reporter concent
rations, repression results. An analysis of c/s requirements revealed that
neither replication nor specific E1-binding sites are required for the init
iators' effect on E2 transactivator function. Though no dependence on E1-bi
nding sites was found, analysis of E1 DNA binding and ATPase mutants reveal
ed 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 doma
in 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 activatio
n domain on DNA. We speculate that E1 may allosterically interact with the
E2 activation domain, perhaps stabilizing a particular structure, which inc
reases the enhancer function of E2. (C) 2000 Academic Press.