A single-codon mutation converts HPV16 E6 oncoprotein into a potential tumor suppressor, which induces p53-dependent senescence of HPV-positive HeLa cervical cancer cells

Oncogene

Volumn 28, Issue 5, 2009, Pages 762-772

  Ristriani, T ^a   Fournane, S ^a   Orfanoudakis, G ^a   Trave G ^a   Masson, M ^a  

^a CNRS   (France)

Author keywords

Cervical cancer; E6 oncoprotein; Human papillomavirus; p53 protein; Senescence

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1; PDZ PROTEIN; PROTEIN E6; PROTEIN P53; SMALL INTERFERING RNA; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; CANCER CELL; CANCER GROWTH; CARCINOGENESIS; CELL PROLIFERATION; CODON; CONTROLLED STUDY; GENE MUTATION; HELA CELL; HUMAN; HUMAN CELL; HUMAN PAPILLOMAVIRUS TYPE 16; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; UBIQUITINATION; UTERINE CERVIX CANCER;

CARCINOMA; CELL AGING; CELL PROLIFERATION; CODON; FEMALE; GENES, DOMINANT; GENES, TUMOR SUPPRESSOR; HELA CELLS; HUMAN PAPILLOMAVIRUS 16; HUMANS; MUTATION; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRUS INFECTIONS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53; UTERINE CERVICAL NEOPLASMS;

HUMAN PAPILLOMAVIRUS; PAPILLOMAVIRIDAE;

EID: 59649123795     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2008.422     Document Type: Article

References (31)

1. Bernard B, Pretet JL, Charlot JF, Mougin C. (2003). Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine-mediated apoptosis. Biol Cell 95:17-26.
2. Butz K, Ristriani T, Hengstermann A, Denk C, Scheffner M, Hoppe-Seyler F. (2003). siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells. Oncogene 22:5938-5945.
3. Courtete J, Sibler AP, Zeder-Lutz G, Dalkara D, Oulad-Abdelghani M, Zuber G et al. (2007). Suppression of cervical carcinoma cell growth by intracytoplasmic codelivery of anti-oncoprotein E6 antibody and small interfering RNA. Mol Cancer Ther 6: 1728-1735.
4. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363-9367.
5. Griffin H, Elston R, Jackson D, Ansell K, Coleman M, Winter G et al. (2006). Inhibition of papillomavirus protein function in cervical cancer cells by intrabody targeting. J Mol Biol 355:360-378.
6. Hall AH, Alexander KA. (2003). RNA interference of human papillomavirus type 18 E6 and E7 induces senescence in HeLa cells. J Virol 77:6066-6069.
7. Horner SM, DeFilippis RA, Manuelidis L, DiMaio D. (2004). Repression of the human papillomavirus E6 gene initiates p53-dependent, telomerase-independent senescence and apoptosis in HeLa cervical carcinoma cells. J Virol 78:4063-4073.
8. Huibregtse JM, Scheffner M, Howley PM. (1991). A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J 10:4129-4135.
9. Johung K, Goodwin EC, DiMaio D. (2007). Human papillomavirus E7 repression in cervical carcinoma cells initiates a transcriptional cascade driven by the retinoblastoma family, resulting in senescence. J Virol 81:2102-2116.
10. Lagrange M, Boulade-Ladame C, Mailly L, Weiss E, Orfanoudakis G, Deryckere F. (2007). Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells. Biochem Biophys Res Commun 361:487-492.
11. Lee CJ, Suh EJ, Kang HT, Im JS, Um SJ, Park JS et al. (2002). Induction of senescence-like state and suppression of telomerase activity through inhibition of HPV E6/E7 gene expression in cells immortalized by HPV16 DNA. Exp Cell Res 277:173-182.
12. Lipari F, McGibbon GA, Wardrop E, Cordingley MG. (2001). Purification and biophysical characterization of a minimal functional domain and of an N-terminal Zn2+-binding fragment from the human papillomavirus type 16 E6 protein. Biochemistry 40: 1196-1204.
13. Liu Y, Chen JJ, Gao Q, Dalal S, Hong Y, Mansur CP et al. (1999). Multiple functions of human papillomavirus type 16 E6 contribute to the immortalization of mammary epithelial cells. J Virol 73: 7297-7307.
14. Livak KJ, Schmittgen TD. (2001). Analysis of relative gene expression data using real time quantitative PCR and the 2(-Delta Delta CT) method. Methods 25:402-408.
15. Massimi P, Gammoh N, Thomas M, Banks L. (2004). HPV E6 specifically targets different cellular pools of its PDZ domain-containing tumour suppressor substrates for proteasome-mediated degradation. Oncogene 23:8033-8039.
16. Masson M, Hindelang C, Sibler AP, Schwalbach G, Trave G, Weiss E. (2003). Preferential nuclear localization of the human papillomavirus type 16 E6 oncoprotein in cervical carcinoma cells. J Gen Virol 84:2099-2104.
17. Nominé Y, Charbonnier S, Ristriani T, Stier G, Masson M, Cavusoglu N et al. (2003). Domain substructure of HPV E6 oncoprotein: biophysical characterization of the E6 C-terminal DNA-binding domain. Biochemistry 42:4909-4917.
18. Nominé Y, Masson M, Charbonnier S, Zanier K, Ristriani T, Deryckere F et al. (2006). Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis. Mol Cell 21:665-678.
19. Nominé Y, Ristriani T, Laurent C, Lefevre JF, Weiss E, Trave G. (2001a). A strategy for optimizing the diversity of fusion proteins: application to purification of recombinant HPV E6 oncoprotein. Protein Eng 14:297-305.
20. Nominé Y, Ristriani T, Laurent C, Lefevre JF, Weiss E, Trave G. (2001b). Formation of soluble inclusion bodies by HPV E6 oncoprotein fused to maltose-binding protein. Protein Exp Purif 23:22-32.
21. Ristriani T, Masson M, Nominé Y, Laurent C, Lefevre JF, Weiss E et al. (2000). HPV oncoprotein E6 is a structure-dependent DNA-binding protein that recognizes four-way junctions. J Mol Biol 296: 1189-1203.
22. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. (1990). The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63: 1129-1136.
23. Stewart D, Kazemi S, Li S, Massimi P, Banks L, Koromilas AE et al. (2004). Ubiquitination and proteasome degradation of the E6 proteins of human papillomavirus type 11 and 18. J Gen Virol 85: 1419-1426.
24. Talis AL, Huibregtse JM, Howley PM. (1998). The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells. J Biol Chem 273:6439-6445.
25. Tang S, Mingfang T, McCoy P, Zheng ZM. (2006). The E7 oncoprotein is translated from spliced E6* transcripts in high-risk human papillomavirus type-16 or type-18 positive cervical cancer cell lines via translation reinitiation. J Virol 80:4249-4263.
26. Töpffer S, Müller-Schiffmann A, Matentzoglu K, Scheffner M, Steger G. (2007). Protein tyrosine phosphatase H1 is a target of the E6 oncoprotein of high-risk genital human paillomaviruses. J Gen Virol 88:2956-2965.
27. Veldman T, Horikawa I, Barrett JC, Schlegel R. (2001). Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16 E6 oncoprotein. J Virol 75:4467-4472.
28. Vousden K. (1993). Interactions of human papillomavirus transforming proteins with the products of tumor suppressor genes. FASEB J 7:872-879.
29. Wells SI, Francis DA, Karpova AY, Dowhanick JJ, Benson JD, Howley PM. (2000). Papillomavirus E2 induces senescence in HPV-positive cells via pRB- and p21(CIP)-dependent pathways. EMBO J 19:5762-5771.
30. Zanier K, Nominé Y, Charbonnier S, Ruhlmann C, Schultz P, Schweizer J et al. (2007). Formation of well-defined soluble aggregates upon fusion to MBP is a generic property of E6 proteins from various human papillomavirus species. Protein Expr Purif 51: 59-70.
31. zur Hausen H. (1996). Papillomavirus infections - a major cause of human cancers. Biochim Biophys Acta 1288:F55-F78.