papillomavirus e7 proteins


Summary: ONCOGENE PROTEINS from papillomavirus that deregulate the CELL CYCLE of infected cells and lead to NEOPLASTIC CELL TRANSFORMATION. Papillomavirus E7 proteins have been shown to interact with various regulators of the cell cycle including RETINOBLASTOMA PROTEIN and certain cyclin-dependent kinase inhibitors.

Top Publications

  1. Toscano Garibay J, Benítez Hess M, Alvarez Salas L. Isolation and characterization of an RNA aptamer for the HPV-16 E7 oncoprotein. Arch Med Res. 2011;42:88-96 pubmed publisher
    ..The affinity and specificity of G5?3N.4 binding domains for the HPV-16 E7 protein may be used for the detection of papillomavirus infection and cervical cancer. ..
  2. Korzeniewski N, Treat B, Duensing S. The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression. Mol Cancer. 2011;10:61 pubmed publisher
  3. Isaacson Wechsler E, Wang Q, Roberts I, Pagliarulo E, Jackson D, Untersperger C, et al. Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia implicates E6/E7 deregulation and the loss of contact inhibition in neoplastic progression. J Virol. 2012;86:6358-64 pubmed publisher
    ..A reduced responsiveness to cell-cell contact inhibition and an increase in E6/E7 activity correlated closely with phenotype. Similar deregulation is likely to underlie the appearance of LSIL or HSIL soon after infection...
  4. Posner M, Lorch J, Goloubeva O, Tan M, Schumaker L, Sarlis N, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol. 2011;22:1071-7 pubmed publisher
    ..These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment. ..
  5. Smith E, Pawlita M, Rubenstein L, Haugen T, Hamsikova E, Turek L. Risk factors and survival by HPV-16 E6 and E7 antibody status in human papillomavirus positive head and neck cancer. Int J Cancer. 2010;127:111-7 pubmed publisher
    ..Differences in antibody status are associated with distinct risk factors and clinical outcomes. This information can be available as a simple blood test at initial presentation, before the removal of tissue through biopsy or surgery. ..
  6. Korzeniewski N, Spardy N, Duensing A, Duensing S. Genomic instability and cancer: lessons learned from human papillomaviruses. Cancer Lett. 2011;305:113-22 pubmed publisher
  7. Yamato K, Egawa N, Endo S, Ui Tei K, Yamada T, Saigo K, et al. Enhanced specificity of HPV16 E6E7 siRNA by RNA-DNA chimera modification. Cancer Gene Ther. 2011;18:587-97 pubmed publisher
    ..Our results show that dsRDC modification enhances the specificity of E6E7 siRNA, which is required for use in in vivo settings...
  8. Pim D, Banks L. Interaction of viral oncoproteins with cellular target molecules: infection with high-risk vs low-risk human papillomaviruses. APMIS. 2010;118:471-93 pubmed publisher
  9. Mattarollo S, Yong M, Gosmann C, Choyce A, Chan D, Leggatt G, et al. NKT cells inhibit antigen-specific effector CD8 T cell induction to skin viral proteins. J Immunol. 2011;187:1601-8 pubmed publisher
    ..Therefore, in the context of viral Ag challenge in the skin, systemic NKT cells limit the capacity for effective priming of adaptive immunity. ..

More Information


  1. Allen C, Lewis J, El Mofty S, Haughey B, Nussenbaum B. Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope. 2010;120:1756-72 pubmed publisher
    ..Understanding the molecular mechanisms behind the improved outcomes in patients with HPV-associated oropharyngeal carcinoma may lead to novel therapeutics for patients with carcinogen-associated carcinomas. ..
  2. Decrausaz L, Revaz V, Bobst M, Corthesy B, Romero P, Nardelli Haefliger D. Induction of human papillomavirus oncogene-specific CD8 T-cell effector responses in the genital mucosa of vaccinated mice. Int J Cancer. 2010;126:2469-78 pubmed publisher
    ..In addition, there was no correlation between the responses measured in blood with those measured in GM, highlighting the necessity and relevance to determine the immune responses in the mucosa where HPV-tumors reside. ..
  3. Laurson J, Khan S, Chung R, Cross K, Raj K. Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein. Carcinogenesis. 2010;31:918-26 pubmed publisher
  4. Moody C, Laimins L. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009;5:e1000605 pubmed publisher
    ..These findings identify a major regulatory mechanism responsible for productive HPV replication in differentiating cells. Our results have potential implications for the development of anti-viral therapies to treat HPV infections...
  5. Guo C, LIU K, Luo H, Chen H, Zheng Y, Sun S, et al. Potent anti-tumor effect generated by a novel human papillomavirus (HPV) antagonist peptide reactivating the pRb/E2F pathway. PLoS ONE. 2011;6:e17734 pubmed publisher
    ..The current study suggests that this specific peptide may serve as a potential therapeutic agent for HPV16-positive cervical cancer. ..
  6. Cardeal L, Boccardo E, Termini L, Rabachini T, Andreoli M, Di Loreto C, et al. HPV16 oncoproteins induce MMPs/RECK-TIMP-2 imbalance in primary keratinocytes: possible implications in cervical carcinogenesis. PLoS ONE. 2012;7:e33585 pubmed publisher
    ..Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome. ..
  7. Barrow Laing L, Chen W, Roman A. Low- and high-risk human papillomavirus E7 proteins regulate p130 differently. Virology. 2010;400:233-9 pubmed publisher
    ..Inhibition of proteasomal degradation extended the half-life of p130, regardless of intracellular localization. These results suggest that there may be divergent mechanisms by which LR and HR HPV E7 target p130 for degradation. ..
  8. McCloskey R, Menges C, Friedman A, Patel D, McCance D. Human papillomavirus type 16 E6/E7 upregulation of nucleophosmin is important for proliferation and inhibition of differentiation. J Virol. 2010;84:5131-9 pubmed publisher
    ..The results show for the first time that NPM is required for the proliferation and inhibition of differentiation observed in HPV E6- and E7-expressing primary cells. ..
  9. Maher D, Bell M, O Donnell E, Gupta B, Jaggi M, Chauhan S. Curcumin suppresses human papillomavirus oncoproteins, restores p53, Rb, and PTPN13 proteins and inhibits benzo[a]pyrene-induced upregulation of HPV E7. Mol Carcinog. 2011;50:47-57 pubmed publisher
    ..These novel findings imply that curcumin may be an effective chemopreventive and therapeutic agent for cervical cancer prevention and treatment. ..
  10. Jabbar S, Strati K, Shin M, Pitot H, Lambert P. Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice. Virology. 2010;407:60-7 pubmed publisher
    ..Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer. ..
  11. Krikelis D, Tzimagiorgis G, Georgiou E, Destouni C, Agorastos T, Haitoglou C, et al. Frequent presence of incomplete HPV16 E7 ORFs in lung carcinomas: memories of viral infection. J Clin Virol. 2010;49:169-74 pubmed publisher
    ..Restriction endonuclease analysis is critical for verifying the reliability of the detection of these sequences. ..
  12. Park J, Pitot H, Strati K, Spardy N, Duensing S, Grompe M, et al. Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res. 2010;70:9959-68 pubmed publisher
    ..These animal studies support the hypotheses that FA patients have increased susceptibility to HPV-associated cancer and that the FA DNA damage response pathway normally attenuates the oncogenic potential of HPV16 E7. ..
  13. Dreier K, Scheiden R, Lener B, Ehehalt D, Pircher H, Muller Holzner E, et al. Subcellular localization of the human papillomavirus 16 E7 oncoprotein in CaSki cells and its detection in cervical adenocarcinoma and adenocarcinoma in situ. Virology. 2011;409:54-68 pubmed publisher
    ..Our findings suggest that the HPV-16 E7 oncoprotein could be a useful marker for the detection of cervical adenocarcinoma and their precursors. ..
  14. Melar New M, Laimins L. Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. J Virol. 2010;84:5212-21 pubmed publisher
    ..We conclude that high levels of miR-203 are inhibitory to HPV amplification and that HPV proteins act to suppress expression of this microRNA to allow productive replication in differentiating cells. ..
  15. Rampias T, Boutati E, Pectasides E, Sasaki C, Kountourakis P, Weinberger P, et al. Activation of Wnt signaling pathway by human papillomavirus E6 and E7 oncogenes in HPV16-positive oropharyngeal squamous carcinoma cells. Mol Cancer Res. 2010;8:433-43 pubmed publisher
    ..In addition, we show the significance of the endogenous Siah-1-dependent ubiquitin/proteasome pathway for beta-catenin degradation and its regulation by E6/E7 viral oncoproteins in HPV16-positive oropharyngeal cancer cells. ..
  16. Mattarollo S, Rahimpour A, Choyce A, Godfrey D, Leggatt G, Frazer I. Invariant NKT cells in hyperplastic skin induce a local immune suppressive environment by IFN-gamma production. J Immunol. 2010;184:1242-50 pubmed publisher
    ..Thus, inhibition of NKT cell recruitment or function may enable effective immunity against tumor and viral Ags expressed in epithelial cells. ..
  17. Kenter G, Welters M, Valentijn A, Lowik M, Berends van der Meer D, Vloon A, et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med. 2009;361:1838-47 pubmed publisher
    ..Complete responses appear to be correlated with induction of HPV-16-specific immunity. ..
  18. Smal C, Alonso L, Wetzler D, Heer A, de Prat Gay G. Ordered self-assembly mechanism of a spherical oncoprotein oligomer triggered by zinc removal and stabilized by an intrinsically disordered domain. PLoS ONE. 2012;7:e36457 pubmed publisher
    ..Finally, its increased immunogenicity related to its supramolecular structure is the basis for the development of a promising therapeutic vaccine candidate for treating HPV cancerous lesions. ..
  19. Faoro V, Barbazza R, Bonin S, Brunetti D, Sulfaro S, Stanta G. Detection of HPV E7 oncoviral protein in cervical lesions by a new antibody. Appl Immunohistochem Mol Morphol. 2013;21:341-50 pubmed publisher
  20. Hong S, Mehta K, Laimins L. Suppression of STAT-1 expression by human papillomaviruses is necessary for differentiation-dependent genome amplification and plasmid maintenance. J Virol. 2011;85:9486-94 pubmed publisher
    ..Overall, our findings demonstrate that suppression of STAT-1 expression by HPV proteins is necessary for genome amplification and maintenance of episomes, suggesting an important role for this activity in viral pathogenesis...
  21. Chemes L, Sánchez I, de Prat Gay G. Kinetic recognition of the retinoblastoma tumor suppressor by a specific protein target. J Mol Biol. 2011;412:267-84 pubmed publisher
    ..We describe the interaction mechanism of Rb with a protein ligand, at the same time an LxCxE-containing model target, and a paradigmatic intrinsically disordered viral oncoprotein. ..
  22. Myklebust M, Bruland O, Fluge Ø, Skarstein A, Balteskard L, Dahl O. MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer. Br J Cancer. 2011;105:1719-25 pubmed publisher
    ..A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells. MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network. ..
  23. Magaldi T, Almstead L, Bellone S, Prevatt E, Santin A, DiMaio D. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation. Virology. 2012;422:114-24 pubmed publisher
    ..These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells...
  24. Roman A, Munger K. The papillomavirus E7 proteins. Virology. 2013;445:138-68 pubmed publisher
    ..This article strives to provide a comprehensive summary of the published research studies on human papillomavirus E7 proteins.
  25. McKenna D, McDade S, Patel D, McCance D. MicroRNA 203 expression in keratinocytes is dependent on regulation of p53 levels by E6. J Virol. 2010;84:10644-52 pubmed publisher
  26. Ghittoni R, Accardi R, Hasan U, Gheit T, Sylla B, Tommasino M. The biological properties of E6 and E7 oncoproteins from human papillomaviruses. Virus Genes. 2010;40:1-13 pubmed publisher
    ..Here, we review most of the findings on the biological properties and molecular mechanisms of the oncoproteins E6 and E7 from mucosal and cutaneous HPV types. ..
  27. Di Bonito P, Grasso F, Mochi S, Petrone L, Fanales Belasio E, Mei A, et al. Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein. Virology. 2009;395:45-55 pubmed publisher
    ..These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity. ..
  28. Haigh O, Kattenbelt J, Cochrane M, Thomson S, Gould A, Tindle R. Hepatitis B surface antigen fusions delivered by DNA vaccination elicit CTL responses to human papillomavirus oncoproteins associated with tumor protection. Cancer Gene Ther. 2010;17:708-20 pubmed publisher
  29. Nicol C, Bunka D, Blair G, Stonehouse N. Effects of single nucleotide changes on the binding and activity of RNA aptamers to human papillomavirus 16 E7 oncoprotein. Biochem Biophys Res Commun. 2011;405:417-21 pubmed publisher
    ..This study demonstrates the potential of aptamers to be highly specific, with small differences in aptamer sequence having profound effects on function. ..
  30. Decrausaz L, Domingos Pereira S, Duc M, Bobst M, Romero P, Schiller J, et al. Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus-associated genital tumors. Int J Cancer. 2011;129:762-72 pubmed publisher
  31. Allison S, Jiang M, Milner J. Oncogenic viral protein HPV E7 up-regulates the SIRT1 longevity protein in human cervical cancer cells. Aging (Albany NY). 2009;1:316-27 pubmed
    ..This link may open the way for a more in-depth understanding of the process of HPV-induced malignant transformation and also of the inter-relationships between aging and cancer. ..
  32. De Vos Van Steenwijk P, Ramwadhdoebe T, Lowik M, van der Minne C, Berends van der Meer D, Fathers L, et al. A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions. Cancer Immunol Immunother. 2012;61:1485-92 pubmed publisher
    ..Thus, vaccination of HSIL patients results in increased HPV16-specific T-cell immunity. Further development of this type of treatment relies on the ability to motivate patients and in the reduction in the side effects. ..
  33. Buonomo T, Carraresi L, Rossini M, Martinelli R. Involvement of aryl hydrocarbon receptor signaling in the development of small cell lung cancer induced by HPV E6/E7 oncoproteins. J Transl Med. 2011;9:2 pubmed publisher
    ..Our results provide the basis for the development of new therapeutic approaches against human SCLC. ..
  34. Di Bonito P, Grasso F, Mangino G, Massa S, Illiano E, Franconi R, et al. Immunomodulatory activity of a plant extract containing human papillomavirus 16-E7 protein in human monocyte-derived dendritic cells. Int J Immunopathol Pharmacol. 2009;22:967-78 pubmed
    ..This is a propaedeutic study for a possible use of E7-containing plant extract in human immunotherapy of HPV-related lesions. ..
  35. Boccardo E, Manzini Baldi C, Carvalho A, Rabachini T, Torres C, Barreta L, et al. Expression of human papillomavirus type 16 E7 oncoprotein alters keratinocytes expression profile in response to tumor necrosis factor-alpha. Carcinogenesis. 2010;31:521-31 pubmed publisher
    ..Further evaluation of the role of such genes in TNF resistance and HPV-associated disease development is warranted...
  36. Hyland P, McDade S, McCloskey R, Dickson G, Arthur K, McCance D, et al. Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes. J Virol. 2011;85:10999-1006 pubmed publisher
  37. Todorovic B, Massimi P, Hung K, Shaw G, Banks L, Mymryk J. Systematic analysis of the amino acid residues of human papillomavirus type 16 E7 conserved region 3 involved in dimerization and transformation. J Virol. 2011;85:10048-57 pubmed publisher
    ..Our results identify several novel E7 mutants that abrogate transformation and also indicate that E7 does not need to exist as a stable dimer in order to transform cells. ..
  38. Cerutti M, Alonso L, Tatti S, de Prat Gay G. Long-lasting immunoprotective and therapeutic effects of a hyperstable E7 oligomer based vaccine in a murine human papillomavirus tumor model. Int J Cancer. 2012;130:1813-20 pubmed publisher
  39. Gyöngyösi E, Szalmás A, Ferenczi A, Konya J, Gergely L, Veress G. Effects of human papillomavirus (HPV) type 16 oncoproteins on the expression of involucrin in human keratinocytes. Virol J. 2012;9:36 pubmed publisher
    ..In contrast, the down-regulation of endogenous IVL expression by HPV16 E7 is probably not caused by a direct and specific effect of E7 on the IVL promoter. ..
  40. Nor Rashid N, Yusof R, Watson R. Disruption of repressive p130-DREAM complexes by human papillomavirus 16 E6/E7 oncoproteins is required for cell-cycle progression in cervical cancer cells. J Gen Virol. 2011;92:2620-7 pubmed publisher
    ..The results show that continued HPV16 E6/E7 expression is necessary in cervical cancer cells to prevent cell-cycle arrest by a repressive p130-DREAM complex...
  41. Bodily J, Mehta K, Laimins L. Human papillomavirus E7 enhances hypoxia-inducible factor 1-mediated transcription by inhibiting binding of histone deacetylases. Cancer Res. 2011;71:1187-95 pubmed publisher
    ..Our findings describe a novel role of the E7 oncoprotein in activating the function of a key transcription factor mediating hypoxic responses by blocking the binding of HDACs. ..
  42. Smal C, Wetzler D, Dantur K, Chemes L, Garcia Alai M, Dellarole M, et al. The human papillomavirus E7-E2 interaction mechanism in vitro reveals a finely tuned system for modulating available E7 and E2 proteins. Biochemistry. 2009;48:11939-49 pubmed publisher
    ..Sequestering E2 into E7-E2 oligomers provides a possible additional route to uncontrolled E7 expression, in addition and prior to the disruption of the E2 gene during viral integration into the host genome. ..
  43. Bester A, Roniger M, Oren Y, Im M, Sarni D, Chaoat M, et al. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell. 2011;145:435-46 pubmed publisher
    ..Our results suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability. ..
  44. Guo C, Liu K, Zheng Y, Luo H, Chen H, Huang L. Apoptosis induced by an antagonist peptide against HPV16 E7 in vitro and in vivo via restoration of p53. Apoptosis. 2011;16:606-18 pubmed publisher
    ..Therefore, this specific peptide may be used to create specific biotherapies for the treatment of HPV 16-positive cervical cancers. ..
  45. Boulenouar S, Weyn C, Van Noppen M, Moussa Ali M, Favre M, Delvenne P, et al. Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells. Carcinogenesis. 2010;31:473-80 pubmed publisher
    ..HPV-16 E5 participated, with E6 and E7, in these changes by impairing E-cadherin expression, a hallmark of malignant progression...
  46. Chemes L, Sánchez I, Smal C, de Prat Gay G. Targeting mechanism of the retinoblastoma tumor suppressor by a prototypical viral oncoprotein. Structural modularity, intrinsic disorder and phosphorylation of human papillomavirus E7. FEBS J. 2010;277:973-88 pubmed publisher
  47. Shin M, Pitot H, Lambert P. Pocket proteins suppress head and neck cancer. Cancer Res. 2012;72:1280-9 pubmed publisher
    ..We conclude that pRb and p107 act together to efficiently suppress head and neck cancer and are, therefore, highly relevant targets of HPV-16 E7 in its contribution to HPV-positive HNSCC. ..
  48. Rampias T, Sasaki C, Weinberger P, Psyrri A. E6 and e7 gene silencing and transformed phenotype of human papillomavirus 16-positive oropharyngeal cancer cells. J Natl Cancer Inst. 2009;101:412-23 pubmed publisher
    ..We examined the effects of repressing E6 and E7 oncogene expression on the transformed phenotype of HPV16-positive oropharyngeal cancer cell lines...
  49. McLaughlin Drubin M, Huh K, Munger K. Human papillomavirus type 16 E7 oncoprotein associates with E2F6. J Virol. 2008;82:8695-705 pubmed publisher
    ..We show that E7-expressing cells show decreased staining for E2F6/polycomb complexes and that this is at least in part dependent on the association with E2F6. ..
  50. Cheng W, Chang M, Sun W, Lee C, Lin H, Su Y, et al. Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism. Gene Ther. 2008;15:1007-16 pubmed publisher
    ..By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy. ..
  51. Balsitis S, Dick F, Dyson N, Lambert P. Critical roles for non-pRb targets of human papillomavirus type 16 E7 in cervical carcinogenesis. Cancer Res. 2006;66:9393-400 pubmed
    ..Together, these data indicate that non-pRb targets of E7 play critical roles in cervical carcinogenesis. ..
  52. Holland D, Hoppe Seyler K, Schuller B, Lohrey C, Maroldt J, Dürst M, et al. Activation of the enhancer of zeste homologue 2 gene by the human papillomavirus E7 oncoprotein. Cancer Res. 2008;68:9964-72 pubmed publisher
    ..Moreover, EZH2 may serve as a novel therapeutic target for the treatment of cervical cancer. ..
  53. De Vos Van Steenwijk P, Piersma S, Welters M, van der Hulst J, Fleuren G, Hellebrekers B, et al. Surgery followed by persistence of high-grade squamous intraepithelial lesions is associated with the induction of a dysfunctional HPV16-specific T-cell response. Clin Cancer Res. 2008;14:7188-95 pubmed publisher