Kaposi's sarcoma-associated herpesvirus open reading frame 50 represses p53-induced transcriptional activity and apoptosis

Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50 (ORF50 ) encodes a viral transcriptional activator which stimulates the transcript ion of viral early and late genes of KSHV. Here we show that ORF50 represse s transcriptional activity of p53 and p53-induced apoptosis through interac tion with CREB binding. protein (CBP). This inhibitory effect of ORF50 on t he transcriptional activity of p53 was relieved by the addition of CBP. ORF 50 mutants, which are defective in interaction with CBP, lost the inhibitor y effects on p53. Our data provide a framework for delineating the regulato ry mechanisms used by KSHV to modulate cellular transcription and the cell cycle.