Journal of Molecular Medicine

, Volume 87, Issue 3, pp 321–331 | Cite as

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

  • Susanne Dymalla
  • Martin Scheffner
  • Elvira Weber
  • Peter Sehr
  • Claudia Lohrey
  • Felix Hoppe-Seyler
  • Karin Hoppe-Seyler
Original Article

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.

Keywords

Human papillomavirus Cervical cancer Cancer therapy Oncogenes 

Notes

Acknowledgements

This work was supported by the Deutsche Krebshilfe. We thank Angela Heilig for excellent technical assistance, Dr. H. Zentgraf for providing anti-hrGFP antibodies and Dr. Jennifer Reed for helpful discussions.

Supplementary material

109_2008_432_MOESM1_ESM.pdf (44 kb)
Fig. S1Total blots obtained by Western blot and used for the indicated figures. Dashed lines indicate where membranes were cut to allow for immunoprinting of a single membrane with different antibodies, as detailed aside. For experimental design, see legends of the indicated figure and methods. a Full scan for Fig. 7a. b Full scan for Fig. 7b. Bold lines indicate which lanes were cut and joined for Fig. 7b. Tubulin immunoblot marked with * was included in Fig. 7b. (PDF 5.03 KB)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Susanne Dymalla
    • 1
  • Martin Scheffner
    • 2
  • Elvira Weber
    • 2
  • Peter Sehr
    • 3
  • Claudia Lohrey
    • 1
  • Felix Hoppe-Seyler
    • 1
  • Karin Hoppe-Seyler
    • 1
  1. 1.Molecular Therapy of Virus-Associated Cancers (F065)German Cancer Research CenterHeidelbergGermany
  2. 2.Department of BiologyUniversity of KonstanzKonstanzGermany
  3. 3.Chemical Biology Core FacilityEMBLHeidelbergGermany

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