Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53

Paola Blanchette, Ying Cheng Chi, Qin Yan, Gary W Ketner, David A. Ornelles, Thomas Dobner, Ronald C. Conaway, Joan Weliky Conaway, Philip E. Branton

Research output: Contribution to journalArticle

Abstract

Small DNA tumor viruses typically encode proteins that either inactivate or degrade p53. Human adenoviruses encode products, including E4orf6 and E1B55K, that do both. Each independently binds to p53 and inhibits its ability to activate gene expression; however, in combination they induce p53 degradation by the ubiquitin pathway. We have shown previously that p53 degradation relies on interactions of E4orf6 with the cellular proteins Cul5, Rbx1, and elongins B and C to form an E3 ligase similar to the SCF and VBC complexes. Here we show that, like other elongin BC-interacting proteins, including elongin A, von Hippel-Lindau protein, and Muf1, the interaction of E4orf6 is mediated by the BC-box motif; however, E4orf6 uniquely utilizes two BC-box motifs for degradation of p53 and another target, Mre11. In addition, our data suggest that the interaction of E1B55K with E4orf6 depends on the ability of E4orf6 to form the E3 ligase complex and that such complex formation may be required for all E4orf6-E1B55K functions.

Original languageEnglish (US)
Pages (from-to)9619-9629
Number of pages11
JournalMolecular and Cellular Biology
Volume24
Issue number21
DOIs
StatePublished - Nov 2004

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Ubiquitin-Protein Ligases
Proteins
DNA Tumor Viruses
Human Adenoviruses
Ubiquitin
Gene Expression
adenovirus E4orf6 protein
elongin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53. / Blanchette, Paola; Chi, Ying Cheng; Yan, Qin; Ketner, Gary W; Ornelles, David A.; Dobner, Thomas; Conaway, Ronald C.; Conaway, Joan Weliky; Branton, Philip E.

In: Molecular and Cellular Biology, Vol. 24, No. 21, 11.2004, p. 9619-9629.

Research output: Contribution to journalArticle

Blanchette, Paola ; Chi, Ying Cheng ; Yan, Qin ; Ketner, Gary W ; Ornelles, David A. ; Dobner, Thomas ; Conaway, Ronald C. ; Conaway, Joan Weliky ; Branton, Philip E. / Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 21. pp. 9619-9629.
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