The anaphase promoting complex: a critical target for viral proteins and anti-cancer drugs.
The study of animal viruses has provided extraordinary insights into cell cycle dynamics and tumor biology. The significance of the p53 and Rb tumor suppressor proteins, for example, was discovered due to their interactions with viral oncogenes. In the past several years, investigations with four viral proteins, human immunodeficiency virus type 1 (HIV-1) vpr, adenovirus E4orf4, chicken anemia virus (CAV) apoptin and human T lymphotropic virus type I (HTLV-I) Tax, have indicated that there are also critical viral targets involved in G2/M control. In particular, recent studies with E4orf4 and apoptin have shown that they induce G2/M arrest by targeting and inhibiting the anaphase-promoting complex/cyclosome (APC/C). Notably, these two viral proteins induce apoptosis selectively in transformed cells in a p53-independent manner; thus pathways affected by these proteins are of significant therapeutic interest. Further investigation of the underlying mechanism of G2/M arrest and subsequent apoptosis induced by viral APC/C inhibitors may shed light on the mechanisms of current cancer therapies and provide the foundation for developing novel therapeutic targets.
Heilman
Destin W
DW
Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Green
Michael R
MR
Teodoro
Jose G
JG
D064173:Anaphase-Promoting Complex-Cyclosome; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D036022:Capsid Proteins / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D016195:G2 Phase; D016356:Gene Products, tax / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes; D014764:Viral Proteins / Q000737:chemistry*
D000970:Antineoplastic Agents; D036022:Capsid Proteins; D016356:Gene Products, tax; D016336:Gene Products, vpr; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C091717:VP3 protein, Chicken anemia virus; D014764:Viral Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome