Skip to main content

Advertisement

SpringerLink
Log in

Modulation of apoptosis by human papillomavirus (HPV) oncoproteins

  • Brief Review
  • Published:
Archives of Virology Aims and scope Submit manuscript

Summary.

The regulation of host-mediated apoptosis by the E6 and E7 oncoproteins has garnered attention because it is believed to be an important strategy employed by high-risk (HR)-human papillomaviruses (HPVs) to evade immune surveillance. Additionally, the revelation that E5 can protect cells from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis suggests that it may also play a role in undermining host defense mechanisms. Cellular transformation is an unintended consequence of persistent infection by HR-HPVs, and it is therefore likely that the primary function of E5, E6 and E7 is to regulate cell survival throughout the normal viral life cycle in order to ensure viral replication and promote the spread of progeny. The purpose of this article is to review the literature on the regulation of host-mediated apoptosis by E5, E6 and E7 that describes the mechanisms employed by HR-HPVs to persist in the host and create the conditions necessary for cellular transformation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • W Al-Saleh P Delvenne JE Arrese AF Nikkels GE Pierard J Boniver (1995) ArticleTitleInverse modulation of intraepithelial Langerhans’ cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix Virchows Arch 427 41–48 Occurrence Handle7551344 Occurrence Handle1:STN:280:BymD3srosVw%3D Occurrence Handle10.1007/BF00203736

    Article  PubMed  CAS  Google Scholar 

  • MJ Antinore MJ Birrer D Patel L Nader DJ McCance (1996) ArticleTitleThe human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors EMBO J 15 1950–1960 Occurrence Handle8617242 Occurrence Handle1:CAS:528:DyaK28XivVantbo%3D

    PubMed  CAS  Google Scholar 

  • GH Ashrafi MR Haghshenas B Marchetti PM O’Brien MS Campo (2005) ArticleTitleE5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I Int J Cancer 113 276–283 Occurrence Handle15386416 Occurrence Handle1:CAS:528:DC%2BD2cXhtFajtLbF Occurrence Handle10.1002/ijc.20558

    Article  PubMed  CAS  Google Scholar 

  • E Berezutskaya S Bagchi (1997) ArticleTitleThe human papillomavirus E7 oncoprotein functionally interacts with the S4 subunit of the 26 S proteasome J Biol Chem 272 30135–30140 Occurrence Handle9374493 Occurrence Handle1:CAS:528:DyaK2sXnslGhtLc%3D Occurrence Handle10.1074/jbc.272.48.30135

    Article  PubMed  CAS  Google Scholar 

  • E Berezutskaya B Yu A Morozov P Raychaudhuri S Bagchi (1997) ArticleTitleDifferential regulation of the pocket domains of the retinoblastoma family proteins by the HPV16 E7 oncoprotein Cell Growth Differ 8 1277–1286 Occurrence Handle9419416 Occurrence Handle1:CAS:528:DyaK2sXotVWlt7g%3D

    PubMed  CAS  Google Scholar 

  • S Blachon S Bellanger C Demeret F Thierry (2005) ArticleTitleNucleo-cytoplasmic shuttling of high risk human Papillomavirus E2 proteins induces apoptosis J Biol Chem 280 36088–36098 Occurrence Handle16135518 Occurrence Handle1:CAS:528:DC%2BD2MXhtFCjtr%2FE Occurrence Handle10.1074/jbc.M505138200

    Article  PubMed  CAS  Google Scholar 

  • HJ Bontkes TD de Gruijl JM Walboomers JT Schiller J Dillner TJ Helmerhorst RH Verheijen RJ Scheper CJ Meijer (1999) ArticleTitleImmune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. II. Systemic but not local IgA responses correlate with clearance of HPV-16 J Gen Virol 80 IssueIDPt 2 409–417 Occurrence Handle10073701 Occurrence Handle1:CAS:528:DyaK1MXhsFChtLc%3D

    PubMed  CAS  Google Scholar 

  • A Brehm SJ Nielsen EA Miska DJ McCance JL Reid AJ Bannister T Kouzarides (1999) ArticleTitleThe E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth EMBO J 18 2449–2458 Occurrence Handle10228159 Occurrence Handle1:CAS:528:DyaK1MXjtlKhs7s%3D Occurrence Handle10.1093/emboj/18.9.2449

    Article  PubMed  CAS  Google Scholar 

  • JJ Chen CE Reid V Band EJ Androphy (1995) ArticleTitleInteraction of papillomavirus E6 oncoproteins with a putative calcium-binding protein Science 269 529–531 Occurrence Handle7624774 Occurrence Handle1:CAS:528:DyaK2MXntF2ksbg%3D Occurrence Handle10.1126/science.7624774

    Article  PubMed  CAS  Google Scholar 

  • SL Chen CH Huang TC Tsai KY Lu YP Tsao (1996) ArticleTitleThe regulation mechanism of c-jun and junB by human papillomavirus type 16 E5 oncoprotein Arch Virol 141 791–800 Occurrence Handle8678826 Occurrence Handle1:CAS:528:DyaK28XksFWnsLs%3D Occurrence Handle10.1007/BF01718155

    Article  PubMed  CAS  Google Scholar 

  • J Cohen (2005) ArticleTitlePublic health. High hopes and dilemmas for a cervical cancer vaccine Science 308 618–621 Occurrence Handle15860602 Occurrence Handle1:CAS:528:DC%2BD2MXjslyjt74%3D Occurrence Handle10.1126/science.308.5722.618

    Article  PubMed  CAS  Google Scholar 

  • M Conrad VJ Bubb R Schlegel (1993) ArticleTitleThe human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein J Virol 67 6170–6178 Occurrence Handle7690419 Occurrence Handle1:CAS:528:DyaK2cXktFCn

    PubMed  CAS  Google Scholar 

  • SA Corden LJ Sant-Cassia AJ Easton AG Morris (1999) ArticleTitleThe integration of HPV-18 DNA in cervical carcinoma Mol Pathol 52 275–282 Occurrence Handle10748877 Occurrence Handle1:CAS:528:DyaK1MXnslGjs7w%3D Occurrence Handle10.1136/mp.52.5.275

    Article  PubMed  CAS  Google Scholar 

  • K Crusius E Auvinen B Steuer H Gaissert A Alonso (1998) ArticleTitleThe human papillomavirus type 16 E5-protein modulates ligand-dependent activation of the EGF receptor family in the human epithelial cell line HaCaT Exp Cell Res 241 76–83 Occurrence Handle9633515 Occurrence Handle1:CAS:528:DyaK1cXjvVGjtL0%3D Occurrence Handle10.1006/excr.1998.4024

    Article  PubMed  CAS  Google Scholar 

  • K Crusius M Kaszkin V Kinzel A Alonso (1999) ArticleTitleThe human papillomavirus type 16 E5 protein modulates phospholipase C-gamma-1 activity and phosphatidyl inositol turnover in mouse fibroblasts Oncogene 18 6714–6718 Occurrence Handle10597278 Occurrence Handle1:CAS:528:DyaK1MXotV2mu7g%3D Occurrence Handle10.1038/sj.onc.1203075

    Article  PubMed  CAS  Google Scholar 

  • K Crusius I Rodriguez A Alonso (2000) ArticleTitleThe human papillomavirus type 16 E5 protein modulates ERK1/2 and p38 MAP kinase activation by an EGFR-independent process in stressed human keratinocytes Virus Genes 20 65–69 Occurrence Handle10766308 Occurrence Handle1:CAS:528:DC%2BD3cXisVSitro%3D Occurrence Handle10.1023/A:1008112207824

    Article  PubMed  CAS  Google Scholar 

  • RA DeFilippis EC Goodwin L Wu D DiMaio (2003) ArticleTitleEndogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells J Virol 77 1551–1563 Occurrence Handle12502868 Occurrence Handle1:CAS:528:DC%2BD3sXitl2ksg%3D%3D Occurrence Handle10.1128/JVI.77.2.1551-1563.2003

    Article  PubMed  CAS  Google Scholar 

  • YY Degenhardt SJ Silverstein (2001) ArticleTitleGps2, a protein partner for human papillomavirus E6 proteins J Virol 75 151–160 Occurrence Handle11119584 Occurrence Handle1:CAS:528:DC%2BD3cXovV2jt7s%3D Occurrence Handle10.1128/JVI.75.1.151-160.2001

    Article  PubMed  CAS  Google Scholar 

  • J Du GG Chen AC Vlantis PK Chan RK Tsang CA van Hasselt (2004) ArticleTitleResistance to apoptosis of HPV 16-infected laryngeal cancer cells is associated with decreased Bak and increased Bcl-2 expression Cancer Lett 205 81–88 Occurrence Handle15036664 Occurrence Handle1:CAS:528:DC%2BD2cXhsVOmt7w%3D Occurrence Handle10.1016/j.canlet.2003.09.035

    Article  PubMed  CAS  Google Scholar 

  • M Du X Fan E Hong JJ Chen (2002) ArticleTitleInteraction of oncogenic papillomavirus E6 proteins with fibulin-1 Biochem Biophys Res Commun 296 962–969 Occurrence Handle12200142 Occurrence Handle1:CAS:528:DC%2BD38XmsV2rs7g%3D Occurrence Handle10.1016/S0006-291X(02)02041-7

    Article  PubMed  CAS  Google Scholar 

  • PJ Duerksen-Hughes J Yang SB Schwartz (1999) ArticleTitleHPV 16 E6 blocks TNF-mediated apoptosis in mouse fibroblast LM cells Virology 264 55–65 Occurrence Handle10544129 Occurrence Handle1:CAS:528:DyaK1MXmvFOlsr0%3D Occurrence Handle10.1006/viro.1999.9977

    Article  PubMed  CAS  Google Scholar 

  • N Dyson PM Howley K Munger E Harlow (1989) ArticleTitleThe human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product Science 243 934–937 Occurrence Handle2537532 Occurrence Handle1:CAS:528:DyaL1MXhslWjs7k%3D Occurrence Handle10.1126/science.2537532

    Article  PubMed  CAS  Google Scholar 

  • M Filippova H Song JL Connolly TS Dermody PJ Duerksen-Hughes (2002) ArticleTitleThe human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis J Biol Chem 277 21730–21739 Occurrence Handle11934887 Occurrence Handle1:CAS:528:DC%2BD38Xksl2jsrY%3D Occurrence Handle10.1074/jbc.M200113200

    Article  PubMed  CAS  Google Scholar 

  • M Filippova L Parkhurst PJ Duerksen-Hughes (2004) ArticleTitleThe human papillomavirus 16 E6 protein binds to Fas-associated death domain and protects cells from Fas-triggered apoptosis J Biol Chem 279 25729–25744 Occurrence Handle15073179 Occurrence Handle1:CAS:528:DC%2BD2cXksFygtL0%3D Occurrence Handle10.1074/jbc.M401172200

    Article  PubMed  CAS  Google Scholar 

  • M Filippova TA Brown-Bryan CA Casiano PJ Duerksen-Hughes (2005) ArticleTitleThe human papillomavirus 16 E6 protein can either protect or further sensitize cells to TNF: effect of dose Cell Death Differ 12 1622–1635 Occurrence Handle1:CAS:528:DC%2BD2MXhtF2ktb7P Occurrence Handle10.1038/sj.cdd.4401678 Occurrence Handle15933739

    Article  CAS  PubMed  Google Scholar 

  • P Finzer A Aguilar-Lemarroy F Rosl (2002) ArticleTitleThe role of human papillomavirus oncoproteins E6 and E7 in apoptosis Cancer Lett 188 15–24 Occurrence Handle12406543 Occurrence Handle1:CAS:528:DC%2BD38Xot1Wqt7s%3D Occurrence Handle10.1016/S0304-3835(02)00431-7

    Article  PubMed  CAS  Google Scholar 

  • N Gammoh HS Grm P Massimi L Banks (2006) ArticleTitleRegulation of human papillomavirus type 16 E7 activity through direct protein interaction with the E2 transcriptional activator J Virol 80 1787–1797 Occurrence Handle16439535 Occurrence Handle1:CAS:528:DC%2BD28XhsFagsr0%3D Occurrence Handle10.1128/JVI.80.4.1787-1797.2006

    Article  PubMed  CAS  Google Scholar 

  • Q Gao S Srinivasan SN Boyer DE Wazer V Band (1999) ArticleTitleThe E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation Mol Cell Biol 19 733–744 Occurrence Handle9858596 Occurrence Handle1:CAS:528:DyaK1MXhvFyjsw%3D%3D

    PubMed  CAS  Google Scholar 

  • Garnett TO, Filippova M, Duerksen-Hughes PJ (2006) Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis. Cell Death Differ [Epub ahead of print] Doi: 10.1038/sj.cdd.4401886

  • U Gaur BB Aggarwal (2003) ArticleTitleRegulation of proliferation, survival and apoptosis by members of the TNF superfamily Biochem Pharmacol 66 1403–1408 Occurrence Handle14555214 Occurrence Handle1:CAS:528:DC%2BD3sXnvVeru7k%3D Occurrence Handle10.1016/S0006-2952(03)00490-8

    Article  PubMed  CAS  Google Scholar 

  • BA Glaunsinger SS Lee M Thomas L Banks R Javier (2000) ArticleTitleInteractions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins Oncogene 19 5270–5280 Occurrence Handle11077444 Occurrence Handle1:CAS:528:DC%2BD3cXosVOitrs%3D Occurrence Handle10.1038/sj.onc.1203906

    Article  PubMed  CAS  Google Scholar 

  • EC Goodwin E Yang CJ Lee HW Lee D DiMaio ES Hwang (2000) ArticleTitleRapid induction of senescence in human cervical carcinoma cells Proc Natl Acad Sci USA 97 10978–10983 Occurrence Handle11005870 Occurrence Handle1:CAS:528:DC%2BD3cXnt1ahsbo%3D Occurrence Handle10.1073/pnas.97.20.10978

    Article  PubMed  CAS  Google Scholar 

  • DR Green (2006) ArticleTitleAt the gates of death Cancer Cell 9 328–330 Occurrence Handle16697952 Occurrence Handle1:CAS:528:DC%2BD28XltF2nsL4%3D Occurrence Handle10.1016/j.ccr.2006.05.004

    Article  PubMed  CAS  Google Scholar 

  • S Gross-Mesilaty E Reinstein B Bercovich KE Tobias AL Schwartz C Kahana A Ciechanover (1998) ArticleTitleBasal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway Proc Natl Acad Sci USA 95 8058–8063 Occurrence Handle9653139 Occurrence Handle1:CAS:528:DyaK1cXks1Slu7k%3D Occurrence Handle10.1073/pnas.95.14.8058

    Article  PubMed  CAS  Google Scholar 

  • AH Hall KA Alexander (2003) ArticleTitleRNA interference of human papillomavirus type 18 E6 and E7 induces senescence in HeLa cells J Virol 77 6066–6069 Occurrence Handle12719599 Occurrence Handle1:CAS:528:DC%2BD3sXjs1Oksbk%3D Occurrence Handle10.1128/JVI.77.10.6066-6069.2003

    Article  PubMed  CAS  Google Scholar 

  • R Herber A Liem H Pitot PF Lambert (1996) ArticleTitleSquamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene J Virol 70 1873–1881 Occurrence Handle8627712 Occurrence Handle1:CAS:528:DyaK28XpvFakug%3D%3D

    PubMed  CAS  Google Scholar 

  • P Hubert SL Giannini A Vanderplasschen E Franzen-Detrooz N Jacobs J Boniver P Delvenne (2001) ArticleTitleDendritic cells induce the death of human papillomavirus-transformed keratinocytes FASEB J 15 2521–2523 Occurrence Handle11641258 Occurrence Handle1:CAS:528:DC%2BD3MXoslSjtLs%3D

    PubMed  CAS  Google Scholar 

  • JM Huibregtse M Scheffner PM Howley (1991) ArticleTitleA cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18 EMBO J 10 4129–4135 Occurrence Handle1661671 Occurrence Handle1:CAS:528:DyaK38Xls1Ggsg%3D%3D

    PubMed  CAS  Google Scholar 

  • MA James JH Lee AJ Klingelhutz (2006) ArticleTitleHuman papillomavirus type 16 E6 activates NF-κB, induces cIAP-2 expression, and protects against apoptosis in a PDZ binding motif-dependent manner J Virol 80 5301–5307 Occurrence Handle16699010 Occurrence Handle1:CAS:528:DC%2BD28XlsVGntLo%3D Occurrence Handle10.1128/JVI.01942-05

    Article  PubMed  CAS  Google Scholar 

  • K Kabsch A Alonso (2002) ArticleTitleThe human papillomavirus type 16 E5 protein impairs TRAIL- and FasL-mediated apoptosis in HaCaT cells by different mechanisms J Virol 76 12162–12172 Occurrence Handle12414956 Occurrence Handle1:CAS:528:DC%2BD38Xos12qtrw%3D Occurrence Handle10.1128/JVI.76.23.12162-12172.2002

    Article  PubMed  CAS  Google Scholar 

  • DW Kaznelson S Bruun A Monrad S Gjerlov J Birk C Ropke B Norrild (2004) ArticleTitleSimultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation Virology 320 301–312 Occurrence Handle15016552 Occurrence Handle1:CAS:528:DC%2BD2cXhvVOqtr4%3D Occurrence Handle10.1016/j.virol.2003.12.018

    Article  PubMed  CAS  Google Scholar 

  • T Kiyono A Hiraiwa M Fujita Y Hayashi T Akiyama M Ishibashi (1997) ArticleTitleBinding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein Proc Natl Acad Sci USA 94 11612–11616 Occurrence Handle9326658 Occurrence Handle1:CAS:528:DyaK2sXmslaqu7s%3D Occurrence Handle10.1073/pnas.94.21.11612

    Article  PubMed  CAS  Google Scholar 

  • C Kuhne L Banks (1998) ArticleTitleE3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box J Biol Chem 273 34302–34309 Occurrence Handle9852095 Occurrence Handle1:CAS:528:DyaK1MXntlWm Occurrence Handle10.1074/jbc.273.51.34302

    Article  PubMed  CAS  Google Scholar 

  • I Kukimoto S Aihara K Yoshiike T Kanda (1998) ArticleTitleHuman papillomavirus oncoprotein E6 binds to the C-terminal region of human minichromosome maintenance 7 protein Biochem Biophys Res Commun 249 258–262 Occurrence Handle9705868 Occurrence Handle1:CAS:528:DyaK1cXlsVWrsrY%3D Occurrence Handle10.1006/bbrc.1998.9066

    Article  PubMed  CAS  Google Scholar 

  • SS Lee RS Weiss RT Javier (1997) ArticleTitleBinding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein Proc Natl Acad Sci USA 94 6670–6675 Occurrence Handle9192623 Occurrence Handle1:CAS:528:DyaK2sXktF2rt7c%3D Occurrence Handle10.1073/pnas.94.13.6670

    Article  PubMed  CAS  Google Scholar 

  • SS Lee B Glaunsinger F Mantovani L Banks RT Javier (2000) ArticleTitleMulti-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 Occurrence Handle11000240 Occurrence Handle1:CAS:528:DC%2BD3cXnt1als7s%3D Occurrence Handle10.1128/JVI.74.20.9680-9693.2000

    Article  PubMed  CAS  Google Scholar 

  • Y Liu V Tergaonkar S Krishna EJ Androphy (1999) ArticleTitleHuman papillomavirus type 16 E6-enhanced susceptibility of L929 cells to tumor necrosis factor alpha correlates with increased accumulation of reactive oxygen species J Biol Chem 274 24819–24827 Occurrence Handle10455154 Occurrence Handle1:CAS:528:DyaK1MXls1ymsrc%3D Occurrence Handle10.1074/jbc.274.35.24819

    Article  PubMed  CAS  Google Scholar 

  • MS Longworth LA Laimins (2004) ArticleTitlePathogenesis of human papillomaviruses in differentiating epithelia Microbiol Mol Biol Rev 68 362–372 Occurrence Handle15187189 Occurrence Handle1:CAS:528:DC%2BD2cXlsl2gsr8%3D Occurrence Handle10.1128/MMBR.68.2.362-372.2004

    Article  PubMed  CAS  Google Scholar 

  • MS Longworth LA Laimins (2004) ArticleTitleThe binding of histone deacetylases and the integrity of zinc finger-like motifs of the E7 protein are essential for the life cycle of human papillomavirus type 31 J Virol 78 3533–3541 Occurrence Handle15016876 Occurrence Handle1:CAS:528:DC%2BD2cXis1Kltbg%3D Occurrence Handle10.1128/JVI.78.7.3533-3541.2004

    Article  PubMed  CAS  Google Scholar 

  • B Mannhardt SA Weinzimer M Wagner M Fiedler P Cohen P Jansen-Durr W Zwerschke (2000) ArticleTitleHuman papillomavirus type 16 E7 oncoprotein binds and inactivates growth-inhibitory insulin-like growth factor binding protein 3 Mol Cell Biol 20 6483–6495 Occurrence Handle10938125 Occurrence Handle1:CAS:528:DC%2BD3cXlvFens78%3D Occurrence Handle10.1128/MCB.20.17.6483-6495.2000

    Article  PubMed  CAS  Google Scholar 

  • F Mantovani L Banks (2001) ArticleTitleThe human papillomavirus E6 protein and its contribution to malignant progression Oncogene 20 7874–7887 Occurrence Handle11753670 Occurrence Handle1:CAS:528:DC%2BD3MXptFCru70%3D Occurrence Handle10.1038/sj.onc.1204869

    Article  PubMed  CAS  Google Scholar 

  • P Massimi D Pim A Storey L Banks (1996) ArticleTitleHPV-16 E7 and adenovirus E1a complex formation with TATA box binding protein is enhanced by casein kinase II phosphorylation Oncogene 12 2325–2330 Occurrence Handle8649772 Occurrence Handle1:CAS:528:DyaK28XjvFCmtL8%3D

    PubMed  CAS  Google Scholar 

  • P Massimi L Banks (2005) ArticleTitleTransformation assays for HPV oncoproteins Methods Mol Med 119 381–395 Occurrence Handle16350412 Occurrence Handle1:CAS:528:DC%2BD2MXhtVektrfP

    PubMed  CAS  Google Scholar 

  • S Mazurek W Zwerschke P Jansen-Durr E Eigenbrodt (2001) ArticleTitleMetabolic cooperation between different oncogenes during cell transformation: interaction between activated ras and HPV-16 E7 Oncogene 20 6891–6898 Occurrence Handle11687968 Occurrence Handle1:CAS:528:DC%2BD3MXot1CitL8%3D Occurrence Handle10.1038/sj.onc.1204792

    Article  PubMed  CAS  Google Scholar 

  • JM Mazzarelli GB Atkins JV Geisberg RP Ricciardi (1995) ArticleTitleThe viral oncoproteins Ad5 E1A, HPV16 E7 and SV40 TAg bind a common egion of the TBP-associated factor-110 Oncogene 11 1859–1864 Occurrence Handle7478615 Occurrence Handle1:CAS:528:DyaK2MXptlOks7k%3D

    PubMed  CAS  Google Scholar 

  • K Munger PM Howley (2002) ArticleTitleHuman papillomavirus immortalization and transformation functions Virus Res 89 213–228 Occurrence Handle12445661 Occurrence Handle1:CAS:528:DC%2BD38XoslGitr4%3D Occurrence Handle10.1016/S0168-1702(02)00190-9

    Article  PubMed  CAS  Google Scholar 

  • S Nakagawa JM Huibregtse (2000) ArticleTitleHuman 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 Occurrence Handle11027293 Occurrence Handle1:CAS:528:DC%2BD3cXnslOjt7s%3D Occurrence Handle10.1128/MCB.20.21.8244-8253.2000

    Article  PubMed  CAS  Google Scholar 

  • ML Nguyen MM Nguyen D Lee AE Griep PF Lambert (2003) ArticleTitleThe PDZ ligand domain of the human papillomavirus type 16 E6 protein is required for E6’s induction of epithelial hyperplasia in vivo J Virol 77 6957–6964 Occurrence Handle12768014 Occurrence Handle1:CAS:528:DC%2BD3sXksFGhs74%3D Occurrence Handle10.1128/JVI.77.12.6957-6964.2003

    Article  PubMed  CAS  Google Scholar 

  • I Oelze J Kartenbeck K Crusius A Alonso (1995) ArticleTitleHuman papillomavirus type 16 E5 protein affects cell-cell communication in an epithelial cell line J Virol 69 4489–4494 Occurrence Handle7769709 Occurrence Handle1:CAS:528:DyaK2MXmt1ags7c%3D

    PubMed  CAS  Google Scholar 

  • JL Parish A Kowalczyk HT Chen GE Roeder R Sessions M Buckle K Gaston (2006) ArticleTitleE2 proteins from high- and low-risk human papillomavirus types differ in their ability to bind p53 and induce apoptotic cell death J Virol 80 4580–4590 Occurrence Handle16611918 Occurrence Handle1:CAS:528:DC%2BD28Xkt1OrsLo%3D Occurrence Handle10.1128/JVI.80.9.4580-4590.2006

    Article  PubMed  CAS  Google Scholar 

  • JS Park EJ Kim HJ Kwon ES Hwang SE Namkoong SJ Um (2000) ArticleTitleInactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis J Biol Chem 275 6764–6769 Occurrence Handle10702232 Occurrence Handle1:CAS:528:DC%2BD3cXhvVGksbk%3D Occurrence Handle10.1074/jbc.275.10.6764

    Article  PubMed  CAS  Google Scholar 

  • DM Parkin F Bray J Ferlay P Pisani (2001) ArticleTitleEstimating the world cancer burden: Globocan 2000 Int J Cancer 94 153–156 Occurrence Handle11668491 Occurrence Handle1:CAS:528:DC%2BD3MXntVGlu78%3D Occurrence Handle10.1002/ijc.1440

    Article  PubMed  CAS  Google Scholar 

  • D Patel SM Huang LA Baglia DJ McCance (1999) ArticleTitleThe E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300 EMBO J 18 5061–5072 Occurrence Handle10487758 Occurrence Handle1:CAS:528:DyaK1MXms1ajsbc%3D Occurrence Handle10.1093/emboj/18.18.5061

    Article  PubMed  CAS  Google Scholar 

  • AC Phillips KH Vousden (1997) ArticleTitleAnalysis of the interaction between human papillomavirus type 16 E7 and the TATA-binding protein, TBP J Gen Virol 78 IssueIDPt 4 905–909 Occurrence Handle9129664 Occurrence Handle1:CAS:528:DyaK2sXisVKqsLw%3D

    PubMed  CAS  Google Scholar 

  • D Pim M Collins L Banks (1992) ArticleTitleHuman papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor Oncogene 7 27–32 Occurrence Handle1311063 Occurrence Handle1:CAS:528:DyaK38XhvVyqsLw%3D

    PubMed  CAS  Google Scholar 

  • D Pim P Massimi SM Dilworth L Banks (2005) ArticleTitleActivation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A Oncogene 24 7830–7838 Occurrence Handle16044149 Occurrence Handle1:CAS:528:DC%2BD2MXht1GisLrJ Occurrence Handle10.1038/sj.onc.1208935

    Article  PubMed  CAS  Google Scholar 

  • P Pisani F Bray DM Parkin (2002) ArticleTitleEstimates of the world-wide prevalence of cancer for 25 sites in the adult population International Journal of Cancer 97 72–81 Occurrence Handle1:CAS:528:DC%2BD3MXovFKrurk%3D Occurrence Handle10.1002/ijc.1571

    Article  CAS  Google Scholar 

  • T Prathapam C Kuhne L Banks (2001) ArticleTitleThe HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity Oncogene 20 7677–7685 Occurrence Handle11753645 Occurrence Handle1:CAS:528:DC%2BD3MXptVGmtLk%3D Occurrence Handle10.1038/sj.onc.1204960

    Article  PubMed  CAS  Google Scholar 

  • LV Ronco AY Karpova M Vidal PM Howley (1998) ArticleTitleHuman papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity Genes Dev 12 2061–2072 Occurrence Handle9649509 Occurrence Handle1:CAS:528:DyaK1cXksFyntbY%3D

    PubMed  CAS  Google Scholar 

  • CM Rudin CB Thompson (1997) ArticleTitleApoptosis and disease: regulation and clinical relevance of programmed cell death Annu Rev Med 48 267–281 Occurrence Handle9046961 Occurrence Handle1:CAS:528:DyaK2sXhtFOjtrs%3D Occurrence Handle10.1146/annurev.med.48.1.267

    Article  PubMed  CAS  Google Scholar 

  • M Scheffner BA Werness JM Huibregtse AJ Levine PM Howley (1990) ArticleTitleThe E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53 Cell 63 1129–1136 Occurrence Handle2175676 Occurrence Handle1:CAS:528:DyaK3MXls12itg%3D%3D Occurrence Handle10.1016/0092-8674(90)90409-8

    Article  PubMed  CAS  Google Scholar 

  • S Song HC Pitot PF Lambert (1999) ArticleTitleThe human papillomavirus type 16 E6 gene alone is sufficient to induce carcinomas in transgenic animals J Virol 73 5887–5893 Occurrence Handle10364340 Occurrence Handle1:CAS:528:DyaK1MXjvFykt7o%3D

    PubMed  CAS  Google Scholar 

  • KS Srivenugopal F Ali-Osman (2002) ArticleTitleThe DNA repair protein, O(6)-methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein Oncogene 21 5940–5945 Occurrence Handle12185595 Occurrence Handle1:CAS:528:DC%2BD38Xmt1WntLs%3D Occurrence Handle10.1038/sj.onc.1205762

    Article  PubMed  CAS  Google Scholar 

  • MH Stoler CR Rhodes A Whitbeck SM Wolinsky LT Chow TR Broker (1992) ArticleTitleHuman papillomavirus type 16 and 18 gene expression in cervical neoplasias Hum Pathol 23 117–128 Occurrence Handle1310950 Occurrence Handle1:STN:280:By2C2Mrms1Y%3D Occurrence Handle10.1016/0046-8177(92)90232-R

    Article  PubMed  CAS  Google Scholar 

  • H Stoppler MC Stoppler E Johnson CM Simbulan-Rosenthal ME Smulson S Iyer DS Rosenthal R Schlegel (1998) ArticleTitleThe E7 protein of human papillomavirus type 16 sensitizes primary human keratinocytes to apoptosis Oncogene 17 1207–1214 Occurrence Handle9771963 Occurrence Handle1:CAS:528:DyaK1cXmt1antrw%3D Occurrence Handle10.1038/sj.onc.1202053

    Article  PubMed  CAS  Google Scholar 

  • MC Stoppler SW Straight G Tsao R Schlegel DJ McCance (1996) ArticleTitleThe E5 gene of HPV-16 enhances keratinocyte immortalization by full-length DNA Virology 223 251–254 Occurrence Handle8806560 Occurrence Handle1:STN:280:BymH3c%2FhvVA%3D Occurrence Handle10.1006/viro.1996.0475

    Article  PubMed  CAS  Google Scholar 

  • SW Straight PM Hinkle RJ Jewers DJ McCance (1993) ArticleTitleThe E5 oncoprotein of human papillomavirus type 16 transforms fibroblasts and effects the downregulation of the epidermal growth factor receptor in keratinocytes J Virol 67 4521–4532 Occurrence Handle8392596 Occurrence Handle1:CAS:528:DyaK3sXmtVSkuro%3D

    PubMed  CAS  Google Scholar 

  • S Tang M Tao JP McCoy SuffixJr ZM Zheng (2006) ArticleTitleThe E7 oncoprotein is translated from spliced E6*I transcripts in high-risk human papillomavirus type 16- or type 18-positive cervical cancer cell lines via translation reinitiation J Virol 80 4249–4263 Occurrence Handle16611884 Occurrence Handle1:CAS:528:DC%2BD28Xkt1Oku74%3D Occurrence Handle10.1128/JVI.80.9.4249-4263.2006

    Article  PubMed  CAS  Google Scholar 

  • M Thomas L Banks (1998) ArticleTitleInhibition of Bak-induced apoptosis by HPV-18 E6 Oncogene 17 2943–2954 Occurrence Handle9881696 Occurrence Handle1:CAS:528:DyaK1MXjtlalug%3D%3D Occurrence Handle10.1038/sj.onc.1202223

    Article  PubMed  CAS  Google Scholar 

  • M Thomas L Banks (1999) ArticleTitleHuman papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types J Gen Virol 80 IssueIDPt 6 1513–1517 Occurrence Handle10374970 Occurrence Handle1:CAS:528:DyaK1MXjs1Omuro%3D

    PubMed  CAS  Google Scholar 

  • M Thomas B Glaunsinger D Pim R Javier L Banks (2001) ArticleTitleHPV E6 and MAGUK protein interactions: determination of the molecular basis for specific protein recognition and degradation Oncogene 20 5431–5439 Occurrence Handle11571640 Occurrence Handle1:CAS:528:DC%2BD3MXntFWjsLk%3D Occurrence Handle10.1038/sj.onc.1204719

    Article  PubMed  CAS  Google Scholar 

  • M Thomas R Laura K Hepner E Guccione C Sawyers L Lasky L Banks (2002) ArticleTitleOncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation Oncogene 21 5088–5096 Occurrence Handle12140759 Occurrence Handle1:CAS:528:DC%2BD38XlsFWrsLo%3D Occurrence Handle10.1038/sj.onc.1205668

    Article  PubMed  CAS  Google Scholar 

  • DA Thompson V Zacny GS Belinsky M Classon DL Jones R Schlegel K Munger (2001) ArticleTitleThe HPV E7 oncoprotein inhibits tumor necrosis factor alpha-mediated apoptosis in normal human fibroblasts Oncogene 20 3629–3640 Occurrence Handle11439326 Occurrence Handle1:CAS:528:DC%2BD3MXltVKnsL4%3D Occurrence Handle10.1038/sj.onc.1204483

    Article  PubMed  CAS  Google Scholar 

  • P Thomsen B van Deurs B Norrild L Kayser (2000) ArticleTitleThe HPV16 E5 oncogene inhibits endocytic trafficking Oncogene 19 6023–6032 Occurrence Handle11146554 Occurrence Handle1:CAS:528:DC%2BD3MXhsFCkuw%3D%3D Occurrence Handle10.1038/sj.onc.1204010

    Article  PubMed  CAS  Google Scholar 

  • L Thyrell O Sangfelt B Zhivotovsky K Pokrovskaja Y Wang S Einhorn D Grander (2005) ArticleTitleThe HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis J Interferon Cytokine Res 25 63–72 Occurrence Handle15695927 Occurrence Handle1:CAS:528:DC%2BD2MXhtVGmtrw%3D Occurrence Handle10.1089/jir.2005.25.63

    Article  PubMed  CAS  Google Scholar 

  • M Tommasino JP Adamczewski F Carlotti CF Barth R Manetti M Contorni F Cavalieri T Hunt L Crawford (1993) ArticleTitleHPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A Oncogene 8 195–202 Occurrence Handle8380917 Occurrence Handle1:CAS:528:DyaK3sXit1yms7w%3D

    PubMed  CAS  Google Scholar 

  • X Tong PM Howley (1997) ArticleTitleThe bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton Proc Natl Acad Sci USA 94 4412–4417 Occurrence Handle9114003 Occurrence Handle1:CAS:528:DyaK2sXjtVykt70%3D Occurrence Handle10.1073/pnas.94.9.4412

    Article  PubMed  CAS  Google Scholar 

  • YP Tsao LY Li TC Tsai SL Chen (1996) ArticleTitleHuman papillomavirus type 11 and 16 E5 represses p21(WafI/SdiI/CipI) gene expression in fibroblasts and keratinocytes J Virol 70 7535–7539 Occurrence Handle8892872 Occurrence Handle1:CAS:528:DyaK28Xmt1Glt7c%3D

    PubMed  CAS  Google Scholar 

  • J Viac Y Chardonnet MC Chignol D Schmitt (1993) ArticleTitlePapilloma viruses, warts, carcinoma and Langerhans cells In Vivo 7 207–212 Occurrence Handle8395234 Occurrence Handle1:STN:280:ByyA28zotFw%3D

    PubMed  CAS  Google Scholar 

  • F Vikhanskaya C Falugi P Valente P Russo (2002) ArticleTitleHuman papillomavirus type 16 E6-enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line Int J Cancer 97 732–739 Occurrence Handle11857347 Occurrence Handle1:CAS:528:DC%2BD38XhtVShsrw%3D Occurrence Handle10.1002/ijc.10114

    Article  PubMed  CAS  Google Scholar 

  • Vogt M, Butz K, Dymalla S, Semzow J, Hoppe-Seyler F (2006) Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein. Oncogene [Epub] Doi: 10.1038/sj.onc.1209429

  • RA Watson M Thomas L Banks S Roberts (2003) ArticleTitleActivity of the human papillomavirus E6 PDZ-binding motif correlates with an enhanced morphological transformation of immortalized human keratinocytes J Cell Sci 116 4925–4934 Occurrence Handle14625386 Occurrence Handle1:CAS:528:DC%2BD2cXhsFOmsQ%3D%3D Occurrence Handle10.1242/jcs.00809

    Article  PubMed  CAS  Google Scholar 

  • MJ Welters A de Jong SJ van den Eeden JM van der Hulst KM Kwappenberg S Hassane KL Franken JW Drijfhout GJ Fleuren G Kenter CJ Melief R Offringa SH van der Burg (2003) ArticleTitleFrequent display of human papillomavirus type 16 E6-specific memory t-Helper cells in the healthy population as witness of previous viral encounter Cancer Res 63 636–641 Occurrence Handle12566307 Occurrence Handle1:CAS:528:DC%2BD3sXosVyisA%3D%3D

    PubMed  CAS  Google Scholar 

  • MJ Welters P van der Logt SJ van den Eeden KM Kwappenberg JW Drijfhout GJ Fleuren GG Kenter CJ Melief SH van der Burg R Offringa (2006) ArticleTitleDetection of human papillomavirus type 18 E6 and E7-specific CD4+ T-helper 1 immunity in relation to health versus disease Int J Cancer 118 950–956 Occurrence Handle16152582 Occurrence Handle1:CAS:528:DC%2BD28Xhtlais7s%3D Occurrence Handle10.1002/ijc.21459

    Article  PubMed  CAS  Google Scholar 

  • BA Werness AJ Levine PM Howley (1990) ArticleTitleAssociation of human papillomavirus types 16 and 18 E6 proteins with p53 Science 248 76–79 Occurrence Handle2157286 Occurrence Handle1:CAS:528:DyaK3cXktF2ltL0%3D Occurrence Handle10.1126/science.2157286

    Article  PubMed  CAS  Google Scholar 

  • H Yuan F Fu J Zhuo W Wang J Nishitani DS An IS Chen X Liu (2005) ArticleTitleHuman papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene expression and confer resistance to apoptosis Oncogene 24 5069–5078 Occurrence Handle15856013 Occurrence Handle1:CAS:528:DC%2BD2MXmsFKrurk%3D Occurrence Handle10.1038/sj.onc.1208691

    Article  PubMed  CAS  Google Scholar 

  • M Zeng A Kumar G Meng Q Gao G Dimri D Wazer H Band V Band (2002) ArticleTitleHuman papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator J Biol Chem 277 45611–45618 Occurrence Handle12235159 Occurrence Handle1:CAS:528:DC%2BD38Xosl2ktr4%3D Occurrence Handle10.1074/jbc.M208447200

    Article  PubMed  CAS  Google Scholar 

  • H Zimmermann R Degenkolbe HU Bernard MJ O’Connor (1999) ArticleTitleThe human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300 J Virol 73 6209–6219 Occurrence Handle10400710 Occurrence Handle1:CAS:528:DyaK1MXksFKnsLw%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.

    T. O. Garnett & P. J. Duerksen-Hughes

Authors
  1. T. O. Garnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. J. Duerksen-Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Garnett, T., Duerksen-Hughes, P. Modulation of apoptosis by human papillomavirus (HPV) oncoproteins. Arch Virol 151, 2321–2335 (2006). https://doi.org/10.1007/s00705-006-0821-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-006-0821-0

Keywords

Search

Navigation