title: Stabilization of p53 in influenza A virus-infected cells is associated with compromised MDM2-mediated ubiquitination of p53.
abstract: Influenza A virus (IAV) induces apoptosis of infected cells. In response to IAV infection, p53, a tumor suppressor involved in regulating apoptosis and host antiviral defense, accumulates and becomes activated. This study was undertaken to examine the mechanism of p53 accumulation in IAV-infected cells. Here we show that p53 accumulation in IAV-infected cells results from protein stabilization, which was associated with compromised Mdm2-mediated ubiquitination of p53. In IAV-infected cells, p53 was stabilized and its half-life was remarkably extended. The ladders of polyubiquitinated p53 were not detectable in the presence of the proteasome inhibitor MG132 and were less sensitive to proteasome-mediated degradation. IAV infection did not affect the abundance of Mdm2, a major ubiquitin E3 ligase responsible for regulating p53 ubiquitination and degradation, but weakened the interaction between p53 and Mdm2. Viral nucleoprotein (NP) was able to increase the transcriptional activity and stability of p53. Furthermore, NP was found to associate with p53 and to impair the p53-Mdm2 interaction and Mdm2-mediated p53 ubiquitination, demonstrating its role in inhibiting Mdm2-mediated p53 ubiquitination and degradation.
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, PR China.
authors.forename: Xiaodu
authors.initials: X
authors.lastname: Wang
authors.forename: Xufang
authors.initials: X
authors.lastname: Deng
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yan
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Zixue
authors.initials: Z
authors.lastname: Shi
authors.forename: Donghua
authors.initials: D
authors.lastname: Shao
authors.forename: Jianchao
authors.initials: J
authors.lastname: Wei
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004285:Dogs; D047468:Immunoprecipitation; D009980:Influenza A virus / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination; D014779:Virus Replication
chemical_list: D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2