Human papillomavirus type 16 E7 oncoprotein inhibits the anaphase promoting complex/cyclosome activity by dysregulating EMI1 expression in mitosis.
The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase complex that orchestrates mitotic progression by targeting key mitotic regulators for proteasomal degradation. APC/C dysfunction is a frequent event during cancer development and can give rise to genomic instability. Here we report that the HPV16 E7 oncoprotein interferes with the degradation of APC/C substrates and that the APC/C inhibitor, EMI1, is expressed at higher levels in HPV16 E7-expressing mitotic cells. HPV16 E7 expression causes increased EMI1 mRNA expression and also inhibits EMI1 degradation. The resulting abnormally high EMI1 levels in HPV16 E7-expressing mitotic cells may inhibit degradation of APC/C substrates and cause the prometaphase delay that we have previously observed in such cells.
Division of Infectious Diseases, Brigham and Women's Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA.
Yueyang
Y
Yu
Karl
K
Munger
D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D044783:F-Box Proteins / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008938:Mitosis; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D059748:Proteolysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D018797:Cell Cycle Proteins; D044783:F-Box Proteins; C498960:FBXO5 protein, human; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome
Anaphase Promoting Complex/Cyclosome (APC/C); Cervical cancer; E7 oncoprotein; EMI1; Genomic instability; Human papillomaviruses; Mitosis