Skip to main content
Article
Conserved region 3 of human papillomavirus 16 E7 contributes to deregulation of the retinoblastoma tumor suppressor
Journal of Virology
  • Biljana Todorovic, Western University
  • Katherine Hung, Western University
  • Paola Massimi, International Centre for Genetic Engineering and Biotechnology
  • Nikita Avvakumov, Western University
  • Frederick A. Dick, London Regional Cancer Program
  • Gary S. Shaw, Western University
  • Lawrence Banks, International Centre for Genetic Engineering and Biotechnology
  • Joe S. Mymryk, Western University
Document Type
Article
Publication Date
12-1-2012
URL with Digital Object Identifier
10.1128/JVI.01637-12
Abstract

The human papillomavirus (HPV) E7 oncoprotein binds cellular factors, preventing or retargeting their function and thereby making the infected cell conducive for viral replication. A key target of E7 is the product of the retinoblastoma susceptibility locus (pRb). This interaction results in the release of E2F transcription factors and drives the host cell into the S phase of the cell cycle. E7 binds pRb via a high-affinity binding site in conserved region 2 (CR2) and also targets a portion of cellular pRb for degradation via the proteasome. Evidence suggests that a secondary binding site exists in CR3, and that this interaction influences pRb deregulation. Additionally, evidence suggests that CR3 also participates in the degradation of pRb. We have systematically analyzed the molecular mechanisms by which CR3 contributes to deregulation of the pRb pathway by utilizing a comprehensive series of mutations in residues predicted to be exposed on the surface of HPV16 E7 CR3. Despite differences in the ability to interact with cullin 2, all CR3 mutants degrade pRb comparably to wild-type E7. We identified two specific patches of residues on the surface of CR3 that contribute to pRb binding independently of the high-affinity CR2 binding site. Mutants within CR3 that affect pRb binding are less effective than the wild-type E7 in overcoming pRb-induced cell cycle arrest. This demonstrates that the interaction between HPV16 E7 CR3 and pRb is functionally important for alteration of the cell cycle. © 2012, American Society for Microbiology.

Citation Information
Biljana Todorovic, Katherine Hung, Paola Massimi, Nikita Avvakumov, et al.. "Conserved region 3 of human papillomavirus 16 E7 contributes to deregulation of the retinoblastoma tumor suppressor" Journal of Virology Vol. 86 Iss. 24 (2012) p. 13313 - 13323
Available at: http://works.bepress.com/frederick-dick/12/