title: Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation.
abstract: Apoptosis has been shown to be induced and downregulated by the Hantaan virus (HTNV) nucleocapsid (N) protein. To address these conflicting data, expression of the p53 protein, one of the key molecules involved in apoptosis, was assessed in the presence of the N protein in A549 and HeLa cells. The amount of p53, increased by drug treatment, was reduced when cells were infected with HTNV or transfected with an expression vector of the HTNV N protein. When cells were treated with a proteasome inhibitor (MG132) or an MDM2 antagonist (Nutlin-3), p53 expression was not reduced in N protein-overexpressed cells. We concluded that the HTNV N protein ubiquitinates and degrades p53 MDM2-dependently. Here we report downregulation of p53 expression through a post-translational mechanism: MDM2-dependent ubiquitination and degradation by the HTNV N protein. These results indicate that N protein-dependent p53 degradation through the ubiquitin proteasome system is one of the anti-apoptotic mechanisms employed by HTNV.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.|Division of Arboviruses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Republic of Korea.
authors.forename: Sun-Whan
authors.initials: SW
authors.lastname: Park
authors.affiliation: Division of Arboviruses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Republic of Korea.
authors.forename: Myung-Guk
authors.initials: MG
authors.lastname: Han
authors.affiliation: Division of Arboviruses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Republic of Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Republic of Korea.
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Ju
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
authors.affiliation: Division of Arboviruses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Republic of Korea.
authors.forename: Jungsang
authors.initials: J
authors.lastname: Ryou
mesh_terms: D017209:Apoptosis; D036022:Capsid Proteins / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016158:Genes, p53; D018063:Hantaan virus / Q000378:metabolism / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D014758:Viral Core Proteins; C111782:nucleocapsid protein, Hantaan virus; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D046988:Proteasome Endopeptidase Complex