Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex

Yoshitaka Sato, Takumi Kamura, Noriko Shirata, Takayuki Murata, Ayumi Kudoh, Satoko Iwahori, Sanae Nakayama, Hiroki Isomura, Yukihiro Nishiyama, Tatsuya Tsurumi

研究成果: Article

69 引用 (Scopus)

抄録

p53-signaling is modulated by viruses to establish a host cellular environment advantageous for their propagation. The Epstein-Barr virus (EBV) lytic program induces phosphorylation of p53, which prevents interaction with MDM2. Here, we show that induction of EBV lytic program leads to degradation of p53 via an ubiquitin-proteasome pathway independent of MDM2. The BZLF1 protein directly functions as an adaptor component of the ECS (Elongin B/C-Cul2/5-SOCS-box protein) ubiquitin ligase complex targeting p53 for degradation. Intringuingly, C-terminal phosphorylation of p53 resulting from activated DNA damage response by viral lytic replication enhances its binding to BZLF1 protein. Purified BZLF1 proteinassociated ECS could be shown to catalyze ubiquitination of phospho-mimetic p53 more efficiently than the wild-type in vitro. The compensation of p53 at middle and late stages of the lytic infection inhibits viral DNA replication and production during lytic infection, suggesting that the degradation of p53 is required for efficient viral propagation. Taken together, these findings demonstrate a role for the BZLF1 protein-associated ECS ligase complex in regulation of p53 phosphorylated by activated DNA damage signaling during viral lytic infection.

元の言語English
記事番号e1000530
ジャーナルPLoS Pathogens
5
発行部数7
DOI
出版物ステータスPublished - 01-07-2009

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Ubiquitin-Protein Ligases
Viral Proteins
Ligases
Ubiquitin
Human Herpesvirus 4
DNA Damage
Suppressor of Cytokine Signaling Proteins
Phosphorylation
Proteins
Ubiquitination
Viral DNA
Virus Diseases
Proteasome Endopeptidase Complex
Infection
DNA Replication
Viruses
elongin

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

これを引用

Sato, Y., Kamura, T., Shirata, N., Murata, T., Kudoh, A., Iwahori, S., ... Tsurumi, T. (2009). Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. PLoS Pathogens, 5(7), [e1000530]. https://doi.org/10.1371/journal.ppat.1000530
Sato, Yoshitaka ; Kamura, Takumi ; Shirata, Noriko ; Murata, Takayuki ; Kudoh, Ayumi ; Iwahori, Satoko ; Nakayama, Sanae ; Isomura, Hiroki ; Nishiyama, Yukihiro ; Tsurumi, Tatsuya. / Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. :: PLoS Pathogens. 2009 ; 巻 5, 番号 7.
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abstract = "p53-signaling is modulated by viruses to establish a host cellular environment advantageous for their propagation. The Epstein-Barr virus (EBV) lytic program induces phosphorylation of p53, which prevents interaction with MDM2. Here, we show that induction of EBV lytic program leads to degradation of p53 via an ubiquitin-proteasome pathway independent of MDM2. The BZLF1 protein directly functions as an adaptor component of the ECS (Elongin B/C-Cul2/5-SOCS-box protein) ubiquitin ligase complex targeting p53 for degradation. Intringuingly, C-terminal phosphorylation of p53 resulting from activated DNA damage response by viral lytic replication enhances its binding to BZLF1 protein. Purified BZLF1 proteinassociated ECS could be shown to catalyze ubiquitination of phospho-mimetic p53 more efficiently than the wild-type in vitro. The compensation of p53 at middle and late stages of the lytic infection inhibits viral DNA replication and production during lytic infection, suggesting that the degradation of p53 is required for efficient viral propagation. Taken together, these findings demonstrate a role for the BZLF1 protein-associated ECS ligase complex in regulation of p53 phosphorylated by activated DNA damage signaling during viral lytic infection.",
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Sato, Y, Kamura, T, Shirata, N, Murata, T, Kudoh, A, Iwahori, S, Nakayama, S, Isomura, H, Nishiyama, Y & Tsurumi, T 2009, 'Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex', PLoS Pathogens, 巻. 5, 番号 7, e1000530. https://doi.org/10.1371/journal.ppat.1000530

Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. / Sato, Yoshitaka; Kamura, Takumi; Shirata, Noriko; Murata, Takayuki; Kudoh, Ayumi; Iwahori, Satoko; Nakayama, Sanae; Isomura, Hiroki; Nishiyama, Yukihiro; Tsurumi, Tatsuya.

:: PLoS Pathogens, 巻 5, 番号 7, e1000530, 01.07.2009.

研究成果: Article

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