p53 and Sp1 cooperate to regulate the expression of Epstein-Barr viral Zta protein.
Epstein-Barr virus (EBV) belongs to the gammaherpesvirus family. To produce infectious progeny, EBV reactivates from latency into the lytic cycle by expressing the determinative lytic transactivator, Zta. In the presence of histone deacetylase inhibitor (HDACi), p53 is a prerequisite for the initiation of the EBV lytic cycle by facilitating the expression of Zta. In this study, a serial mutational analysis of Zta promoter (Zp) indicated an important role for the ZID element in responding to HDACi induction and p53 binds to this ZID element together with Sp1, a universal transcription factor. Abolition of the DNA-binding ability of Sp1 reduces the inducibility of ZID by HDACi and also reduces the amount of p53 binding to ZID. Finally, it was shown that EBV in p53-positive-lymphoblastoid cell lines (LCLs) can enter into the lytic cycle spontaneously; however, knockdown of p53 in LCLs leads to retardation of EBV reactivation.
College of Medicine, Graduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.
Huey-Huey
HH
Chua
Hsin-Yi
HY
Chiu
Sue-Jane
SJ
Lin
Pei-Lun
PL
Weng
Jiun-Han
JH
Lin
Shao-Wen
SW
Wu
Shu-Chun
SC
Tsai
Ching-Hwa
CH
Tsai
D002460:Cell Line; D004252:DNA Mutational Analysis; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation
C063676:BZLF1 protein, Herpesvirus 4, Human; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53