Human papillomavirus type 16 E7 oncoprotein inhibits the anaphase promoting complex/cyclosome activity by

Yueyang Yu1, Karl Munger

  • 1Division of Infectious Diseases, Brigham and Women's Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA.

Virology
|October 1, 2013
PubMed

Insights

The human papillomavirus (HPV) 16 E7 oncoprotein disrupts cell division by increasing levels of the APC/C inhibitor EMI1. This leads to impaired degradation of key cell cycle proteins, causing mitotic errors and genomic instability in cancer.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Virology

Background:

  • The anaphase-promoting complex/cyclosome (APC/C) is a crucial ubiquitin ligase regulating mitosis.
  • APC/C dysfunction contributes to genomic instability and cancer development.
  • Human papillomavirus (HPV) oncoproteins are implicated in cervical cancer pathogenesis.

Purpose of the Study:

  • To investigate the mechanism by which HPV16 E7 oncoprotein affects APC/C activity.
  • To determine the role of the APC/C inhibitor EMI1 in HPV16 E7-mediated cellular effects.

Main Methods:

  • Analysis of APC/C substrate degradation in HPV16 E7-expressing cells.
  • Quantification of EMI1 mRNA and protein levels.
  • Assessment of mitotic progression and prometaphase delay.

Main Results:

  • HPV16 E7 expression interferes with the degradation of APC/C substrates.
  • EMI1 levels are significantly elevated in HPV16 E7-expressing mitotic cells.
  • HPV16 E7 inhibits both EMI1 mRNA degradation and protein degradation, leading to accumulation.

Conclusions:

  • HPV16 E7 oncoprotein dysregulates mitosis by increasing EMI1 levels.
  • Elevated EMI1 inhibits APC/C activity, leading to prometaphase delay and potential genomic instability.
  • This mechanism highlights a novel pathway through which HPV contributes to cancer development.

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