Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency.
The p53 tumor suppressor protein, which is commonly mutated in human cancers, has been shown to interact directly with virally encoded from papillomavirus, adenovirus, and simian virus 40. The disruption of p53 function may be required for efficient replication of certain viruses and may also play a role in the development of virally induced malignancies. Infection with Epstein-Barr virus (EBV) has been associated with the development of B-cell lymphomas and nasopharyngeal carcinoma. Here we show that the EBV immediate-early protein, BZLF1 (Z), which is responsible for initiating the switch from latent to lytic infection, can interact directly in vitro and in vivo with the tumor suppressor protein, p53. This interaction requires the coiled-coil dimerization domain of the Z protein and the carboxy-terminal portion of p53. Overexpression of wild-type p53 inhibits the ability of Z to disrupt viral latency. Likewise, Z inhibits p53-dependent transactivation in lymphoid cells. The direct interaction between Z and p53 may play a role in regulating the switch from latent to lytic viral infection.
Zhang
Q
Q
Department of Medicine, University of North Carolina at Chapel Hill 27599.
Gutsch
D
D
Kenney
S
S
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D017735:Virus Latency
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins