Viral Inhibition of the Anaphase-Promoting Complex/Cyclosome as a

Mechanism of Tumor-specific Cell Death

Jose G. Teodoro, Ph.DMcGill Cancer Center

Department of BiochemistryMcGill UniversityMontréal, Canada

Viruses as tools in the study of cell transformation and apoptosis

Viruses as tools in the study of cell transformation and apoptosis

Apoptin localizes in a transformation-dependent manner

Apoptin localization is regulated by a factor in transformed cells

Proteomic analysis of Apoptin-associated proteins

Subunit structure of the APC/C

Thornton et al.Genes & Dev (2006)

Apoptin induces destabilization of the APC/C

FPLC analysis

Apoptin colocalizes with APC/C within PML bodies

Apoptin colocalizes with APC/C within PML bodies

Tran et al. J Virol. 2007 Oct 17

Overview and future directions

How does G2/M arrest proceed to apoptosis?Do current chemotherapies rely on APC/C inhibition for efficacy?Can the APC/C be an anti-cancer drug target?

Acknowledgements

McGill University

Isabelle GamacheMohamed MustafaRussell TowersSarah AssadianYiqing LuMichael Hell

U Mass

Michael GreenDestin HeilmanAlbert ParkerJulie Zhou

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Reagents

Frank GrahamCrister Hoog