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Human papillomavirus type 16 E7 oncoprotein binds and inactivates growth-inhibitory insulin-like growth factor binding protein 3.
Mannhardt, B; Weinzimer, S A; Wagner, M; Fiedler, M; Cohen, P; Jansen-Dürr, P; Zwerschke, W.
Affiliation
  • Mannhardt B; Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, INF 242, D-69120 Heidelberg, Germany.
Mol Cell Biol ; 20(17): 6483-95, 2000 Sep.
Article in En | MEDLINE | ID: mdl-10938125
The E7 protein encoded by human papillomavirus type 16 is one of the few viral genes that can immortalize primary human cells and thereby override cellular senescence. While it is generally assumed that this property of E7 depends on its interaction with regulators of the cell cycle, we show here that E7 targets insulin-like growth factor binding protein 3 (IGFBP-3), the product of a p53-inducible gene that is overexpressed in senescent cells. IGFBP-3 can suppress cell proliferation and induce apoptosis; we show here that IGFBP-3-mediated apoptosis is inhibited by E7, which binds to IGFBP-3 and triggers its proteolytic cleavage. Two transformation-deficient mutants of E7 failed to inactivate IGFBP-3, suggesting that inactivation of IGFBP-3 may contribute to cell transformation.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oncogene Proteins, Viral / Insulin-Like Growth Factor Binding Protein 3 Limits: Humans Language: En Journal: Mol Cell Biol Year: 2000 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oncogene Proteins, Viral / Insulin-Like Growth Factor Binding Protein 3 Limits: Humans Language: En Journal: Mol Cell Biol Year: 2000 Document type: Article