The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53.
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.
Howard Hughes Medical Institute, Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester 01605, USA.
Jose G
JG
Teodoro
Destin W
DW
Heilman
Albert E
AE
Parker
Michael R
MR
Green
D064173:Anaphase-Promoting Complex-Cyclosome; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D036022:Capsid Proteins / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D011233:Precipitin Tests; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
C577335:ANAPC1 protein, human; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D036022:Capsid Proteins; D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; C091717:VP3 protein, Chicken anemia virus; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome