The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53

Jose G. Teodoro; Destin W. Heilman; Albert E. Parker; Michael R. Green

doi:10.1101/gad.1198404

The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53

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

Abstract

The chicken anemia virus protein Apoptin induces apoptosis in the absence of p53 by a mechanism that remains to be elucidated. Here we show that in transformed cells, Apoptin is associated with APC1, a subunit of the anaphase-promoting complex/cyclosome (APC/C). We demonstrate that Apoptin expression, or depletion of APC1 by RNA interference, inhibits APC/C function in p53 null cells, resulting in G2/M arrest and apoptosis. Our results explain the ability of Apoptin to induce apoptosis in the absence of p53 and suggest that the APC/C is an attractive target for anticancer drug development.

Keywords

Footnotes

Supplemental material is available at http://www.genesdev.org.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1198404.
↵1 These authors contributed equally to this work.
↵2 Corresponding author. E-MAIL michael.green{at}umassmed.edu; FAX (508) 856-5473.
- Accepted June 21, 2004.
- Received February 25, 2004.
Cold Spring Harbor Laboratory Press