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 transcription of viral early and late genes of KSHV. Here we show that ORF50 represses transcriptional activity of p53 and p53-induced apoptosis through interaction with CREB binding protein (CBP). This inhibitory effect of ORF50 on the transcriptional activity of p53 was relieved by the addition of CBP. ORF50 mutants, which are defective in interaction with CBP, lost the inhibitory effects on p53. Our data provide a framework for delineating the regulatory mechanisms used by KSHV to modulate cellular transcription and the cell cycle.
Gwack
Y
Y
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Hwang
S
S
Byun
H
H
Lim
C
C
Kim
J W
JW
Choi
E J
EJ
Choe
J
J
D017209:Apoptosis; D050882:CREB-Binding Protein; D019288:Herpesvirus 8, Human / Q000235:genetics*; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000502:physiology*
D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D050882:CREB-Binding Protein