E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway

Sarah N. Boyer, David E. Wazer, Vimla Band

Research output: Contribution to journalArticle

661 Citations (Scopus)

Abstract

Rb protein is a critical regulator of entry into the cell cycle, and loss of Rb function by deletions, mutations, or interaction with DNA viral oncoproteins leads to oncogenic transformation. We have shown that the human papilloma virus (HPV)-16 E7 gene is sufficient to induce the immortalization of mammary epithelial cells (MECs). Surprisingly, the steady-state level of Rb protein in these immortal cells was drastically decreased. Here, we used pulse-chase analysis to show that the in vivo loss of Rb protein in E7- immortalized MECs is a consequence of enhanced degradation. Expression of HPV16 E7 in a cell line with a temperature-sensitive mutation in the E1 enzyme of the ubiquitin pathway demonstrated that degradation of Rb was ubiquitin dependent. Treatment of E7-immortalized MECs with aldehyde inhibitors of proteasome-associated proteases led to a marked stabilization of Rb protein, particularly the hypophosphorylated form. Taken together, our results provide evidence for HPV-16 E7-induced enhanced degradation of Rb protein via a ubiquitin-proteasome pathway and suggest a second mechanism of oncogenic transformation by E7, in addition to its previously identified ability to sequester Rb from E2F. Our analyses also show that normal Rb levels are regulated by the ubiquitin-proteasome degradation pathway.

Original languageEnglish (US)
Pages (from-to)4620-4624
Number of pages5
JournalCancer Research
Volume56
Issue number20
StatePublished - Oct 15 1996

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Papillomaviridae
Retinoblastoma Protein
Proteasome Endopeptidase Complex
Ubiquitin
Breast
Epithelial Cells
Proteins
Proteasome Inhibitors
Sequence Deletion
Oncogene Proteins
Viral DNA
Aldehydes
Cell Cycle
Peptide Hydrolases
Cell Line
Mutation
Temperature
Enzymes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. / Boyer, Sarah N.; Wazer, David E.; Band, Vimla.

In: Cancer Research, Vol. 56, No. 20, 15.10.1996, p. 4620-4624.

Research output: Contribution to journalArticle

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