The HPV16 E6 Oncoprotein Causes Prolonged Receptor Protein Tyrosine Kinase Signaling and Enhances Internalization of Phosphorylated Receptor Species

PLoS Pathogens

Volumn 9, Issue 3, 2013, Pages

  Spangle, Jennifer M ^a   Munger, Karl ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; HUMAN PAPILLOMAVIRUS TYPE 16 E6 PROTEIN; INSULIN RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; ONCOPROTEIN; PHOSPHATASE; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; SOMATOMEDIN RECEPTOR; UNCLASSIFIED DRUG; E6 PROTEIN, HUMAN PAPILLOMAVIRUS TYPE 16; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; REPRESSOR PROTEIN; TARGET OF RAPAMYCIN KINASE;

ARTICLE; CELL MIGRATION; CONTROLLED STUDY; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE MICROSCOPY; INTERNALIZATION; NEWBORN; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; WESTERN BLOTTING; WOUND HEALING; BIOLOGICAL MODEL; CELL LINE; CELL MOTION; CYTOLOGY; FEMALE; GENETICS; HUMAN PAPILLOMAVIRUS TYPE 16; KERATINOCYTE; MALE; METABOLISM; PAPILLOMAVIRUS INFECTION; PHOSPHORYLATION; PHYSIOLOGY; UTERINE CERVIX TUMOR; VIROLOGY;

HUMAN PAPILLOMAVIRUS;

CELL LINE; CELL MOVEMENT; FEMALE; HUMAN PAPILLOMAVIRUS 16; HUMANS; INFANT, NEWBORN; KERATINOCYTES; MALE; MODELS, BIOLOGICAL; MULTIPROTEIN COMPLEXES; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRUS INFECTIONS; PHOSPHORYLATION; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, INSULIN; RECEPTORS, SOMATOMEDIN; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; UTERINE CERVICAL NEOPLASMS;

EID: 84875990922     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003237     Document Type: Article

References (58)

1. McLaughlin-Drubin ME, Munger K, (2009) Oncogenic activities of human papillomaviruses. Virus Res 143: 195-208.
2. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM, (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75: 495-505.
3. Gardiol D, Kuhne C, Glaunsinger B, Lee SS, Javier R, et al. (1999) Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 18: 5487-5496.
4. Glaunsinger BA, Lee SS, Thomas M, Banks L, Javier R, (2000) Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins. Oncogene 19: 5270-5280.
5. Jing M, Bohl J, Brimer N, Kinter M, Vande Pol SB, (2007) Degradation of tyrosine phosphatase PTPN3 (PTPH1) by association with oncogenic human papillomavirus E6 proteins. J Virol 81: 2231-2239.
6. Kiyono T, Hiraiwa A, Fujita M, Hayashi Y, Akiyama T, et al. (1997) Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94: 11612-11616.
7. Lee SS, Glaunsinger B, Mantovani F, Banks L, Javier RT, (2000) Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. J Virol 74: 9680-9693.
8. Lee SS, Weiss RS, Javier RT, (1997) Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94: 6670-6675.
9. Nakagawa S, Huibregtse JM, (2000) Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 20: 8244-8253.
10. Spanos WC, Hoover A, Harris GF, Wu S, Strand GL, et al. (2008) The PDZ binding motif of human papillomavirus type 16 E6 induces PTPN13 loss, which allows anchorage-independent growth and synergizes with ras for invasive growth. J Virol 82: 2493-2500.
11. Klingelhutz AJ, Foster SA, McDougall JK, (1996) Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380: 79-82.
12. Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, et al. (1999) Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci U S A 96: 1291-1296.
13. Zhou X, Munger K, (2009) Expression of the human papillomavirus type 16 E7 oncoprotein induces an autophagy-related process and sensitizes normal human keratinocytes to cell death in response to growth factor deprivation. Virology 385: 192-197.
14. Eichten A, Rud DS, Grace M, Piboonniyom SO, Zacny V, et al. (2004) Molecular pathways executing the "trophic sentinel" response in HPV-16 E7-expressing normal human diploid fibroblasts upon growth factor deprivation. Virology 319: 81-93.
15. Evan GI, Vousden KH, (2001) Proliferation, cell cycle and apoptosis in cancer. Nature 411: 342-348.
16. Spangle JM, Munger K, (2010) The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis. J Virol 84: 9398-9407.
17. Lu Z, Hu X, Li Y, Zheng L, Zhou Y, et al. (2004) Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin. J Biol Chem 279: 35664-35670.
18. Zhou X, Spangle JM, Munger K, (2009) Expression of a viral oncoprotein in normal human epithelial cells triggers an autophagy-related process: is autophagy an "Achilles' heel" of human cancers? Autophagy 5: 578-579.
19. Fernandes H, Cohen S, Bishayee S, (2001) Glycosylation-induced conformational modification positively regulates receptor-receptor association: a study with an aberrant epidermal growth factor receptor (EGFRvIII/DeltaEGFR) expressed in cancer cells. J Biol Chem 276: 5375-5383.
20. Rojas M, Yao S, Lin YZ, (1996) Controlling epidermal growth factor (EGF)-stimulated Ras activation in intact cells by a cell-permeable peptide mimicking phosphorylated EGF receptor. J Biol Chem 271: 27456-27461.
21. Levkowitz G, Waterman H, Ettenberg SA, Katz M, Tsygankov AY, et al. (1999) Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell 4: 1029-1040.
22. Hernandez-Sanchez C, Blakesley V, Kalebic T, Helman L, LeRoith D, (1995) The role of the tyrosine kinase domain of the insulin-like growth factor-I receptor in intracellular signaling, cellular proliferation, and tumorigenesis. J Biol Chem 270: 29176-29181.
23. White MF, Shoelson SE, Keutmann H, Kahn CR, (1988) A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor. J Biol Chem 263: 2969-2980.
24. Sigismund S, Argenzio E, Tosoni D, Cavallaro E, Polo S, et al. (2008) Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev Cell 15: 209-219.
25. Wang Q, Villeneuve G, Wang Z, (2005) Control of epidermal growth factor receptor endocytosis by receptor dimerization, rather than receptor kinase activation. EMBO Rep 6: 942-948.
26. McCormack SJ, Brazinski SE, Moore JL Jr, Werness BA, Goldstein DJ, (1997) Activation of the focal adhesion kinase signal transduction pathway in cervical carcinoma cell lines and human genital epithelial cells immortalized with human papillomavirus type 18. Oncogene 15: 265-274.
27. Vande Pol SB, Brown MC, Turner CE, (1998) Association of Bovine Papillomavirus Type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16: 43-52.
28. Petersen CP, Bordeleau ME, Pelletier J, Sharp PA, (2006) Short RNAs repress translation after initiation in mammalian cells. Mol Cell 21: 533-542.
29. Yu CF, Liu ZX, Cantley LG, (2002) ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase. J Biol Chem 277: 19382-19388.
30. Wang Z, Moran MF, (1996) Requirement for the adapter protein GRB2 in EGF receptor endocytosis. Science 272: 1935-1939.
31. Romeo Y, Zhang X, Roux PP, (2012) Regulation and function of the RSK family of protein kinases. Biochem J 441: 553-569.
32. Zhou H, Huang S, (2010) mTOR signaling in cancer cell motility and tumor metastasis. Crit Rev Eukaryot Gene Expr 20: 1-16.
33. Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, et al. (2007) NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128: 129-139.
34. Lobo GP, Waite KA, Planchon SM, Romigh T, Houghton JA, et al. (2008) ATP modulates PTEN subcellular localization in multiple cancer cell lines. Hum Mol Genet 17: 2877-2885.
35. Contreras-Paredes A, De la Cruz-Hernandez E, Martinez-Ramirez I, Duenas-Gonzalez A, Lizano M, (2009) E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway. Virology 383: 78-85.
36. Zhou Y, Pan Y, Zhang S, Shi X, Ning T, et al. (2007) Increased phosphorylation of p70 S6 kinase is associated with HPV16 infection in cervical cancer and esophageal cancer. Br J Cancer 97: 218-222.
37. McCloskey R, Menges C, Friedman A, Patel D, McCance DJ, (2010) Human papillomavirus type 16 E6/E7 upregulation of nucleophosmin is important for proliferation and inhibition of differentiation. J Virol 84: 5131-5139.
38. Hoover AC, Strand GL, Nowicki PN, Anderson ME, Vermeer PD, et al. (2009) Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway. Oncogene 28: 3960-3970.
39. Akerman GS, Tolleson WH, Brown KL, Zyzak LL, Mourateva E, et al. (2001) Human papillomavirus type 16 E6 and E7 cooperate to increase epidermal growth factor receptor (EGFR) mRNA levels, overcoming mechanisms by which excessive EGFR signaling shortens the life span of normal human keratinocytes. Cancer Res 61: 3837-3843.
40. Sizemore N, Choo CK, Eckert RL, Rorke EA, (1998) Transcriptional regulation of the EGF receptor promoter by HPV16 and retinoic acid in human ectocervical epithelial cells. Exp Cell Res 244: 349-356.
41. Johnston D, Hall H, DiLorenzo TP, Steinberg BM, (1999) Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas. Cancer Res 59: 968-974.
42. Goh LK, Huang F, Kim W, Gygi S, Sorkin A, Multiple mechanisms collectively regulate clathrin-mediated endocytosis of the epidermal growth factor receptor. J Cell Biol 189: 871-883.
43. Batzer AG, Rotin D, Urena JM, Skolnik EY, Schlessinger J, (1994) Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol 14: 5192-5201.
44. Skolnik EY, Batzer A, Li N, Lee CH, Lowenstein E, et al. (1993) The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science 260: 1953-1955.
45. Bazenet CE, Gelderloos JA, Kazlauskas A, (1996) Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation. Mol Cell Biol 16: 6926-6936.
46. Pratt RL, Kinch MS, (2002) Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade. Oncogene 21: 7690-7699.
47. Talbert-Slagle K, DiMaio D, (2009) The bovine papillomavirus E5 protein and the PDGF beta receptor: it takes two to tango. Virology 384: 345-351.
48. Kaplan DR, Whitman M, Schaffhausen B, Pallas DC, White M, et al. (1987) Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell 50: 1021-1029.
49. Whitman M, Kaplan DR, Schaffhausen B, Cantley L, Roberts TM, (1985) Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 315: 239-242.
50. Ichaso N, Dilworth SM, (2001) Cell transformation by the middle T-antigen of polyoma virus. Oncogene 20: 7908-7916.
51. Summers SA, Lipfert L, Birnbaum MJ, (1998) Polyoma middle T antigen activates the Ser/Thr kinase Akt in a PI3-kinase-dependent manner. Biochem Biophys Res Commun 246: 76-81.
52. Shuda M, Kwun HJ, Feng H, Chang Y, Moore PS, (2011) Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. J Clin Invest 9: 3623-3634.
53. Halbert CL, Demers GW, Galloway DA, (1992) The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells. J Virol 66: 2125-2134.
54. Baker SJ, Markowitz S, Fearon ER, Willson JK, Vogelstein B, (1990) Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249: 912-915.
55. Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R, (1989) The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63: 4417-4421.
56. Spangle JM, Ghosh-Choudhury N, Munger K, (2012) Activation of cap-dependent translation by mucosal human papillomavirus E6 proteins is dependent on the integrity of the LXXLL binding motif. J Virol 14: 7466-7472.
57. Sedman SA, Barbosa MS, Vass WC, Hubbert NL, Haas JA, et al. (1991) The full-length E6 protein of human papillomavirus type 16 has transforming and trans-activating activities and cooperates with E7 to immortalize keratinocytes in culture. J Virol 65: 4860-4866.
58. McLaughlin-Drubin ME, Huh KW, Munger K, (2008) Human papillomavirus type 16 E7 oncoprotein associates with E2F6. J Virol 82: 8695-8705.