The anaphase promoting complex: a critical target for viral proteins and anti-cancer drugs

Destin W Heilman1, Michael R Green, Jose G Teodoro

  • 1Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Insights

Viral proteins targeting the anaphase-promoting complex/cyclosome (APC/C) induce cell cycle arrest and apoptosis. These findings offer new therapeutic targets for cancer treatment, particularly in p53-independent pathways.

Area of Science:

  • Virology
  • Cell Biology
  • Cancer Biology

Background:

  • Animal viruses have historically illuminated fundamental cellular processes, including cell cycle regulation and tumor development.
  • The roles of tumor suppressors p53 and Rb were initially uncovered through their interactions with viral oncogenes.
  • Recent research highlights viral proteins impacting G2/M cell cycle control, including HIV-1 vpr, adenovirus E4orf4, CAV apoptin, and HTLV-I Tax.

Purpose of the Study:

  • To investigate the mechanisms by which viral proteins E4orf4 and apoptin induce G2/M cell cycle arrest.
  • To explore the selective induction of apoptosis in transformed cells by these viral proteins.
  • To identify potential therapeutic strategies targeting viral-induced cell cycle disruption in cancer.

Main Methods:

  • Investigated the interaction of viral proteins E4orf4 and apoptin with cellular targets.
  • Analyzed the induction of G2/M cell cycle arrest mediated by these viral proteins.
  • Assessed the induction of apoptosis in cancer cells in a p53-independent manner.

Main Results:

  • Adenovirus E4orf4 and chicken anemia virus apoptin were shown to inhibit the anaphase-promoting complex/cyclosome (APC/C).
  • These viral proteins induce G2/M cell cycle arrest by targeting the APC/C.
  • E4orf4 and apoptin selectively trigger apoptosis in transformed cells, independent of p53 function.

Conclusions:

  • Viral proteins targeting the APC/C represent a significant mechanism for inducing G2/M arrest and apoptosis.
  • The p53-independent induction of apoptosis by these viral proteins presents promising therapeutic avenues for cancer treatment.
  • Understanding these viral pathways can inform the development of novel anti-cancer therapies and enhance existing treatment strategies.

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