Myxoma virus M11L prevents apoptosis through constitutive interaction with Bak

Gen Wang, John W. Barrett, Steven H. Nazarian, Helen Everett, Xiujuan Gao, Chris Bleackley, Karen Colwill, Michael F. Moran, Grant McFadden

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

M11L, a 166-amino-acid antiapoptotic protein of myxoma virus, was previously shown to bind to the peripheral benzodiazepine receptor by hydrophobic interactions at the outer mitochondrial membrane. Here we demonstrate that an additional property of M11L is the ability to constitutively form inhibitory complexes with the proapoptotic Bcl-2 family member Bak in human cells. This binding interaction was identified by both FLAG-tagged pull-down assays and tandem affinity purification from transfected and virus-infected human cells. M11L binds constitutively to human Bak and, under some inducible conditions, to human Bax as well, but not to the other Bcl-2 family members (Bad, Bid, Bcl-2). When stably expressed in human embryonic kidney (HEK293) cells, M11L effectively protects these cells from Fas ligand-induced apoptosis, thereby blocking release of cytochrome c, activation of caspase 9, and cleavage of poly(ADP-ribose) polymerase. We also demonstrate in coexpression studies that M11L can interact with Bak independently of any involvement with Bax. Furthermore, cells stably expressing M11L function to prevent apoptosis that is induced by overexpression of Bak. We conclude that M11L inhibits, in a species-independent fashion, apoptotic signals mediated by activation of Bak.

Original languageEnglish (US)
Pages (from-to)7097-7111
Number of pages15
JournalJournal of virology
Volume78
Issue number13
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Wang, G., Barrett, J. W., Nazarian, S. H., Everett, H., Gao, X., Bleackley, C., Colwill, K., Moran, M. F., & McFadden, G. (2004). Myxoma virus M11L prevents apoptosis through constitutive interaction with Bak. Journal of virology, 78(13), 7097-7111. https://doi.org/10.1128/JVI.78.13.7097-7111.2004