A novel peptide motif binding to and blocking the intracellular activity of the human papillomavirus E6 oncoprotein

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2009
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Dymalla, Susanne
Weber, Elvira
Sehr, Peter
Lohrey, Claudia
Hoppe-Seyler, Felix
Hoppe-Seyler, Karin
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Journal of Molecular Medicine ; 87 (2009), 3. - pp. 321-331. - ISSN 0946-2716. - eISSN 1432-1440
Abstract
Specific types of human papillomaviruses (HPVs) cause cervical cancer. The viral E6 oncogene is a critical factor for maintaining the malignant phenotype of HPV-positive tumour cells. By yeast two-hybrid screening of a randomised peptide expression library, we isolated linear short peptides, which specifically bind to the HPV16 E6 oncoprotein. Sequence alignments and mutational analyses of the peptides identified a hitherto undiscovered E6-binding motif. Intracellular expression of a peptide containing the novel E6-binding motif resulted in inhibition of colony formation capacity, specifically of HPV16-positive cancer cells. A solubility-optimised variant of the peptide was created, which binds to HPV16 E6 with high affinity. Its intracellular expression efficiently induced apoptosis in HPV16-positive cancer cells. This was linked to restoration of intracellular p53 activities. Thus, this newly identified E6-binding motif could form a novel basis for the development of rational strategies for the treatment of HPV16-positive preneoplastic and neoplastic lesions.
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570 Biosciences, Biology
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ISO 690DYMALLA, Susanne, Martin SCHEFFNER, Elvira WEBER, Peter SEHR, Claudia LOHREY, Felix HOPPE-SEYLER, Karin HOPPE-SEYLER, 2009. A novel peptide motif binding to and blocking the intracellular activity of the human papillomavirus E6 oncoprotein. In: Journal of Molecular Medicine. 87(3), pp. 321-331. ISSN 0946-2716. eISSN 1432-1440. Available under: doi: 10.1007/s00109-008-0432-1
BibTex
@article{Dymalla2009novel-1248,
  year={2009},
  doi={10.1007/s00109-008-0432-1},
  title={A novel peptide motif binding to and blocking the intracellular activity of the human papillomavirus E6 oncoprotein},
  number={3},
  volume={87},
  issn={0946-2716},
  journal={Journal of Molecular Medicine},
  pages={321--331},
  author={Dymalla, Susanne and Scheffner, Martin and Weber, Elvira and Sehr, Peter and Lohrey, Claudia and Hoppe-Seyler, Felix and Hoppe-Seyler, Karin}
}
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