Human Cytomegalovirus IE1-72 Protein Interacts with p53 and Inhibits p53-Dependent Transactivation by a Mechanism Different from That of IE2-86 Protein

摘要: Infection of host cells with human cytomegalovirus (HCMV) induces cell cycle dysregulation. Two HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, are promiscuous transactivators that have been implicated in the dysregulatory events. Cellular p53 protein is accumulated to high levels HCMV-infected cells, but indicative marker transcriptional activity, p21, markedly decreased. Both IE2-86 were able transactivate promoter interact DNA-transfected or cells. UL84, a multiregulatory expressed early periods infection, also interacted p53. prevented disrupted binding p53-specific DNA sequences, while and/or UL84 enhanced induced supershift this DNA-protein complex. inhibit p53-dependent activation plasmid-transfected IE1-72, rather than was found be responsible for p21 downregulation HEL transfection analysis using mutants revealed exon 2/3 zinc finger region essential IE1-72's effect on repression activation. These data suggest transactivates accumulation, represses transactivation activity by unique hindrance mechanism different from IE2-86. Thus, various modes viral IE proteins interactions might result multiple outcomes, such as stimulation cellular synthesis, progression arrest, prevention program death.