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The adenovirus E4orf6 E3 ubiquitin ligase complex assembles in a novel fashion

Chi Ying Cheng1, Paola Blanchette, Philip E Branton

  • 1Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.

Virology
|March 21, 2007
PubMed

Insights

Human adenovirus E4orf6 protein utilizes a novel E3 ubiquitin ligase complex to degrade p53. This complex, involving Cul5 and Elongins, assembles uniquely, differing from known cellular E3 ligases.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Adenovirus E4orf6 and E1B55K proteins form an E3 ubiquitin ligase complex.
  • This complex targets cellular proteins like p53 and Mre11 for degradation.
  • Previous studies identified Cul5, Rbx1, Elongin B, and C as components interacting with E4orf6.

Purpose of the Study:

  • To investigate the functional significance of BC-box motifs in the E4orf6 complex.
  • To identify the mechanism of Cul5 selection by E4orf6.
  • To understand the novel assembly of this E3 ubiquitin ligase complex.

Main Methods:

  • Analysis of E4orf6 protein interactions.
  • Identification and functional testing of BC-box motifs.
  • Cul5 protein knockdown experiments.
  • Genetic analysis of potential Cul5-binding motifs.

Main Results:

  • A third functional BC-box motif in E4orf6 was identified.
  • Cul5 protein levels are essential for p53 degradation.
  • A sequence homologous to the 'Cul5 box motif' in E4orf6 does not mediate Cul5 binding or p53 degradation.
  • E4orf6 employs a distinct mechanism for Cul5 selection.

Conclusions:

  • Adenovirus E4orf6 assembles a unique E3 ubiquitin ligase complex with Elongins and Cul5.
  • The assembly mechanism differs significantly from known Cullin-containing E3 ligases.
  • E4orf6 utilizes a novel strategy for Cul5 recruitment, distinct from the 'Cul5 box motif'.

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