KEGG PATHWAY: ko05165

PATHWAY: ko05165

Entry

ko05165                     Pathway

Name

Human papillomavirus infection

Description

Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus. HPV infect mucoal and cutaneous epithelium resulting in several types of pathologies, most notably, cervical cancer. All types of HPV share a common genomic structure and encode eight proteins: E1, E2, E4, E5, E6, and E7 (early) and L1 and L2 (late). It has been demonstrated that E1 and E2 are involved in viral transcription and replication. The functions of the E4 protein is not yet fully understood. E5, E6, and E7 act as oncoproteins. E5 inhibits the V-ATPase, prolonging EGFR signaling and thereby promoting cell proliferation. The expression of E6 and E7 not only inhibits the tumor suppressors p53 and Rb, but also alters additional signalling pathways. Among these pathways, PI3K/Akt signalling cascade plays a very important role in HPV-induced carcinogenesis. The L1 and L2 proteins form icosahedral capsids for progeny virion generation.

Class

Human Diseases; Infectious disease: viral

Pathway map

ko05165

Human papillomavirus infection

Drug

D02783

Afovirsen sodium (USAN)

D06555

Amolimogene bepiplasmid (USAN)

D06666

Verpasep caltespen (USAN/INN)

Orthology

K03209

wingless-type MMTV integration site family, member 1

K00182

wingless-type MMTV integration site family, member 2

K00312

wingless-type MMTV integration site family, member 3

K00408

wingless-type MMTV integration site family, member 4

K00444

wingless-type MMTV integration site family, member 5

K00445

wingless-type MMTV integration site family, member 6

K00572

wingless-type MMTV integration site family, member 7

K00714

wingless-type MMTV integration site family, member 8

K01064

wingless-type MMTV integration site family, member 9

K01357

wingless-type MMTV integration site family, member 10

K01384

wingless-type MMTV integration site family, member 11

K01558

wingless-type MMTV integration site family, member 16

K02432

frizzled 1/7

K02235

frizzled 2

K02329

frizzled 3

K02354

frizzled 4

K02375

frizzled 5/8

K02376

frizzled 6

K02842

frizzled 9/10

K02353

segment polarity protein dishevelled

K21807

Alphapapillomavirus protein E6

K03083

glycogen synthase kinase 3 beta [EC:2.7.11.26]

K02157

axin 1

K04385

axin 2

K02085

adenomatosis polyposis coli protein

K02105

catenin beta 1

K08957

casein kinase 1, alpha [EC:2.7.11.1]

K11126

telomerase reverse transcriptase [EC:2.7.7.49]

K02620

transcription factor 7

K04490

transcription factor 7-like 1

K04491

transcription factor 7-like 2

K10587

ubiquitin-protein ligase E3 A [EC:2.3.2.26]

K05401

toll-like receptor 3

K05842

toll-like receptor adapter molecule 1

K03174

TNF receptor-associated factor 3

K07211

inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]

K05410

TANK-binding kinase 1 [EC:2.7.11.10]

K05411

interferon regulatory factor 3

K05415

interferon beta

K04498

E1A/CREB-binding protein [EC:2.3.1.48]

K11315

transcriptional adapter 3

K04451

tumor protein p53

K19260

Papillomaviridae major capsid protein L1

K21808

Alphapapillomavirus minor capsid protein L2

K05631

atrophin-1 interacting protein 3 (BAI1-associated protein 1)

K01110

phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]

K04237

partitioning defective protein 3

K06093

partitioning defective protein 6

K06069

atypical protein kinase C iota type [EC:2.7.11.13]

K18952

atypical protein kinase C zeta type [EC:2.7.11.13]

K04393

cell division control protein 42

K16175

protein scribble

K12076

disks large protein 1

K12075

discs large protein 2

K21098

discs large protein 3

K06094

lethal(2) giant larvae protein

K06090

crumbs 3

K06092

InaD-like protein

K06091

MAGUK p55 subfamily member 5

K03900

von Willebrand factor

K16857

thrombospondin 1

K04659

thrombospondin 2/3/4/5

K05717

fibronectin 1

K06236

collagen type I alpha

K19719

collagen type II alpha

K06237

collagen type IV alpha

K06238

collagen type VI alpha

K08131

collagen type IX alpha

K05637

laminin, alpha 1/2

K06240

laminin, alpha 3/5

K06241

laminin, alpha 4

K05636

laminin, beta 1

K06243

laminin, beta 2

K06244

laminin, beta 3

K06245

laminin, beta 4

K05635

laminin, gamma 1

K06246

laminin, gamma 2

K06247

laminin, gamma 3

K06248

chondroadherin

K06249

reelin [EC:3.4.21.-]

K06250

secreted phosphoprotein 1

K06251

vitronectin

K06252

tenascin

K06253

integrin binding sialoprotein

K06480

integrin alpha 1

K06481

integrin alpha 2

K06476

integrin alpha 2B

K06482

integrin alpha 3

K06483

integrin alpha 4

K06484

integrin alpha 5

K06485

integrin alpha 6

K06583

integrin alpha 7

K06584

integrin alpha 8

K06585

integrin alpha 9

K06586

integrin alpha 10

K06587

integrin alpha 11

K06487

integrin alpha V

K05719

integrin beta 1

K06493

integrin beta 3

K06525

integrin beta 4

K06588

integrin beta 5

K06589

integrin beta 6

K06590

integrin beta 7

K06591

integrin beta 8

K05725

focal adhesion kinase 1 [EC:2.7.10.2]

K05760

paxillin

K03156

tumor necrosis factor superfamily, member 2

K03158

tumor necrosis factor receptor superfamily member 1A

K03171

tumor necrosis factor receptor type 1-associated DEATH domain protein

K04389

tumor necrosis factor ligand superfamily member 6

K04390

tumor necrosis factor receptor superfamily member 6

K02373

FAS-associated death domain protein

K04398

caspase 8 [EC:3.4.22.61]

K02187

caspase 3 [EC:3.4.22.56]

K13365

sodium/hydrogen exchange regulatory cofactor NHE-RF1

K21809

Alphapapillomavirus protein E7

K04382

serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]

K03456

serine/threonine-protein phosphatase 2A regulatory subunit A

K04354

serine/threonine-protein phosphatase 2A regulatory subunit B

K11583

serine/threonine-protein phosphatase 2A regulatory subunit B''

K11584

serine/threonine-protein phosphatase 2A regulatory subunit B'

K07206

tuberous sclerosis 1

K07207

tuberous sclerosis 2

K07208

Ras homolog enriched in brain

K07203

serine/threonine-protein kinase mTOR [EC:2.7.11.1]

K07205

eukaryotic translation initiation factor 4E binding protein 1

K04688

ribosomal protein S6 kinase beta [EC:2.7.11.1]

K21810

Alphapapillomavirus replication protein E1 [EC:5.6.2.-]

K21811

Alphapapillomavirus regulatory protein E2

K14021

Bcl-2 homologous antagonist/killer

K02158

Bcl-2-antagonist of cell death

K05089

platelet-derived growth factor receptor beta [EC:2.7.10.1]

K00922

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K02649

phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K04456

RAC serine/threonine-protein kinase [EC:2.7.11.1]

K07201

forkhead box protein O1

K21812

Alphapapillomavirus protein E5

K06624

cyclin-dependent kinase inhibitor 1B

K06625

cyclin-dependent kinase inhibitor 1A

K04503

G1/S-specific cyclin-D1

K10151

G1/S-specific cyclin-D2

K10152

G1/S-specific cyclin-D3

K02089

cyclin-dependent kinase 4 [EC:2.7.11.22]

K02091

cyclin-dependent kinase 6 [EC:2.7.11.22]

K06626

G1/S-specific cyclin-E1

K02206

cyclin-dependent kinase 2 [EC:2.7.11.22]

K06618

retinoblastoma-associated protein

K04681

retinoblastoma-like protein 1

K16332

retinoblastoma-like protein 2

K03062

26S proteasome regulatory subunit T2

K17454

transcription factor E2F1

K06627

cyclin-A

K04728

serine-protein kinase ATM [EC:2.7.11.1]

K06640

serine/threonine-protein kinase ATR [EC:2.7.11.1]

K05448

vascular endothelial growth factor A

K04467

inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]

K07209

inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]

K07210

inhibitor of nuclear factor kappa-B kinase subunit gamma

K02580

nuclear factor NF-kappa-B p105 subunit

K04735

transcription factor p65

K06643

E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]

K12236

transcriptional repressor NF-X1

K06067

histone deacetylase 1/2 [EC:3.5.1.98]

K11643

chromodomain-helicase-DNA-binding protein 4 [EC:5.6.2.-]

K09444

interferon regulatory factor 1

K03120

transcription initiation factor TFIID TATA-box-binding protein

K06751

MHC class I antigen

K14009

B-cell receptor-associated protein 31

K02145

V-type H+-transporting ATPase subunit A [EC:7.1.2.2]

K02147

V-type H+-transporting ATPase subunit B

K02148

V-type H+-transporting ATPase subunit C

K02149

V-type H+-transporting ATPase subunit D

K02150

V-type H+-transporting ATPase subunit E

K02151

V-type H+-transporting ATPase subunit F

K02152

V-type H+-transporting ATPase subunit G

K02144

V-type H+-transporting ATPase subunit H

K02154

V-type H+-transporting ATPase subunit a

K02146

V-type H+-transporting ATPase subunit d

K02153

V-type H+-transporting ATPase subunit e

K02155

V-type H+-transporting ATPase 16kDa proteolipid subunit

K03661

V-type H+-transporting ATPase 21kDa proteolipid subunit

K03662

V-type H+-transporting ATPase S1 subunit

K04357

epidermal growth factor

K04361

epidermal growth factor receptor [EC:2.7.10.1]

K04364

growth factor receptor-bound protein 2

K03099

son of sevenless

K02833

GTPase HRas

K07827

GTPase KRas

K07828

GTPase NRas

K04366

RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04368

mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K11987

prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]

K04261

prostaglandin E receptor 4

K04632

guanine nucleotide-binding protein G(s) subunit alpha

K04345

protein kinase A [EC:2.7.11.11]

K02159

apoptosis regulator BAX

K05870

cyclic AMP-responsive element-binding protein 1

K09048

cyclic AMP-responsive element-binding protein 3

K09047

cyclic AMP-responsive element-binding protein 5

K10691

E3 ubiquitin-protein ligase UBR4 [EC:2.3.2.27]

K10389

tubulin gamma

K00873

pyruvate kinase [EC:2.7.1.40]

K05414

interferon alpha

K05130

interferon receptor 1

K05131

interferon receptor 2

K11217

Janus kinase 1 [EC:2.7.10.2]

K11219

non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]

K11220

signal transducer and activator of transcription 1

K11221

signal transducer and activator of transcription 2

K04693

interferon regulatory factor 9

K16195

eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1]

K14608

2'-5'-oligoadenylate synthase-like protein

K14754

interferon-induced GTP-binding protein Mx

K12159

ubiquitin cross-reactive protein

K06052

jagged-1

K02599

Notch 1

K20994

Notch 2

K20995

Notch 3

K20996

Notch 4

K04505

presenilin 1 [EC:3.4.23.-]

K05948

fringe [EC:2.4.1.222]

K06061

mastermind

K06053

recombining binding protein suppressor of hairless

K06054

hairy and enhancer of split 1

K09087

hairy and enhancer of split 2/6/7

K09088

hairy and enhancer of split 3

K09089

hairy and enhancer of split 4

K06055

hairy and enhancer of split 5

K09091

hairy and enhancer of split related with YRPW motif

Compound

C00575

3',5'-Cyclic AMP

C00584

Prostaglandin E2

C05981

Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:20592731

Authors

Moody CA, Laimins LA

Title

Human papillomavirus oncoproteins: pathways to transformation.

Journal

Nat Rev Cancer 10:550-60 (2010)
DOI:10.1038/nrc2886

Reference

PMID:25752815

Authors

Chen J

Title

Signaling pathways in HPV-associated cancers and therapeutic implications.

Journal

Rev Med Virol 25 Suppl 1:24-53 (2015)
DOI:10.1002/rmv.1823

Reference

PMID:26008697

Authors

Tummers B, Burg SH

Title

High-risk human papillomavirus targets crossroads in immune signaling.

Journal

Viruses 7:2485-506 (2015)
DOI:10.3390/v7052485

Reference

PMID:19684440

Authors

Lehoux M, D'Abramo CM, Archambault J

Title

Molecular mechanisms of human papillomavirus-induced carcinogenesis.

Journal

Public Health Genomics 12:268-80 (2009)
DOI:10.1159/000214918

Reference

PMID:23164805

Authors

Pang CL, Thierry F

Title

Human papillomavirus proteins as prospective therapeutic targets.

Journal

Microb Pathog 58:55-65 (2013)
DOI:10.1016/j.micpath.2012.11.002

Reference

PMID:19156753

Authors

Yugawa T, Kiyono T

Title

Molecular mechanisms of cervical carcinogenesis by high-risk human papillomaviruses: novel functions of E6 and E7 oncoproteins.

Journal

Rev Med Virol 19:97-113 (2009)
DOI:10.1002/rmv.605

Reference

PMID:17645777

Authors

Narisawa-Saito M, Kiyono T

Title

Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins.

Journal

Cancer Sci 98:1505-11 (2007)
DOI:10.1111/j.1349-7006.2007.00546.x

Reference

PMID:11486705

Authors

Wolf JK, Ramirez PT.

Title

The molecular biology of cervical cancer.

Journal

Cancer Invest 19:621-9 (2001)
DOI:10.1081/CNV-100104290

Reference

PMID:10793105

Authors

zur Hausen H

Title

Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis.

Journal

J Natl Cancer Inst 92:690-8 (2000)
DOI:10.1093/jnci/92.9.690

Reference

PMID:16259056

Authors

Kim YT, Zhao M

Title

Aberrant cell cycle regulation in cervical carcinoma.

Journal

Yonsei Med J 46:597-613 (2005)
DOI:10.3349/ymj.2005.46.5.597

Reference

PMID:15956361

Authors

McCance DJ

Title

Human papillomaviruses and cell signaling.

Journal

Sci STKE 2005:pe29 (2005)
DOI:10.1126/stke.2882005pe29

Reference

PMID:15342967

Authors

Motoyama S, Ladines-Llave CA, Luis Villanueva S, Maruo T

Title

The role of human papilloma virus in the molecular biology of cervical carcinogenesis.

Journal

Kobe J Med Sci 50:9-19 (2004)

Reference

PMID:24316445

Authors

Tommasino M

Title

The human papillomavirus family and its role in carcinogenesis.

Journal

Semin Cancer Biol 26:13-21 (2014)
DOI:10.1016/j.semcancer.2013.11.002

Reference

PMID:26295406

Authors

Bello JO, Nieva LO, Paredes AC, Gonzalez AM, Zavaleta LR, Lizano M

Title

Regulation of the Wnt/beta-Catenin Signaling Pathway by Human Papillomavirus E6 and E7 Oncoproteins.

Journal

Viruses 7:4734-55 (2015)
DOI:10.3390/v7082842

Reference

PMID:26289783

Authors

Shah M, Anwar MA, Park S, Jafri SS, Choi S

Title

In silico mechanistic analysis of IRF3 inactivation and high-risk HPV E6 species-dependent drug response.

Journal

Sci Rep 5:13446 (2015)
DOI:10.1038/srep13446

Reference

PMID:26797638

Authors

James CD, Roberts S

Title

Viral Interactions with PDZ Domain-Containing Proteins-An Oncogenic Trait?

Journal

Pathogens 5:E8 (2016)
DOI:10.3390/pathogens5010008

Reference

PMID:26147797

Authors

Ganti K, Broniarczyk J, Manoubi W, Massimi P, Mittal S, Pim D, Szalmas A, Thatte J, Thomas M, Tomaic V, Banks L

Title

The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy.

Journal

Viruses 7:3530-51 (2015)
DOI:10.3390/v7072785

Reference

PMID:21954943

Authors

Subbaiah VK, Kranjec C, Thomas M, Banks L

Title

PDZ domains: the building blocks regulating tumorigenesis.

Journal

Biochem J 439:195-205 (2011)
DOI:10.1042/BJ20110903

Reference

PMID:23175122

Authors

Banks L, Pim D, Thomas M

Title

Human tumour viruses and the deregulation of cell polarity in cancer.

Journal

Nat Rev Cancer 12:877-86 (2012)
DOI:10.1038/nrc3400

Reference

PMID:19029942

Authors

Thomas M, Narayan N, Pim D, Tomaic V, Massimi P, Nagasaka K, Kranjec C, Gammoh N, Banks L

Title

Human papillomaviruses, cervical cancer and cell polarity.

Journal

Oncogene 27:7018-30 (2008)
DOI:10.1038/onc.2008.351

Reference

PMID:19901438

Authors

Jayshree RS, Sreenivas A, Tessy M, Krishna S

Title

Cell intrinsic & extrinsic factors in cervical carcinogenesis.

Journal

Indian J Med Res 130:286-95 (2009)

Reference

PMID:16862386

Authors

Garnett TO, Duerksen-Hughes PJ

Title

Modulation of apoptosis by human papillomavirus (HPV) oncoproteins.

Journal

Arch Virol 151:2321-35 (2006)
DOI:10.1007/s00705-006-0821-0

Reference

PMID:26022660

Authors

Zhang L, Wu J, Ling MT, Zhao L, Zhao KN

Title

The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses.

Journal

Mol Cancer 14:87 (2015)
DOI:10.1186/s12943-015-0361-x

Reference

PMID:22078316

Authors

Venuti A, Paolini F, Nasir L, Corteggio A, Roperto S, Campo MS, Borzacchiello G

Title

Papillomavirus E5: the smallest oncoprotein with many functions.

Journal

Mol Cancer 10:140 (2011)
DOI:10.1186/1476-4598-10-140

Reference

PMID:11753669

Authors

DiMaio D, Mattoon D

Title

Mechanisms of cell transformation by papillomavirus E5 proteins.

Journal

Oncogene 20:7866-73 (2001)
DOI:10.1038/sj.onc.1204915

Reference

PMID:22262402

Authors

Ganguly N

Title

Human papillomavirus-16 E5 protein: oncogenic role and therapeutic value.

Journal

Cell Oncol (Dordr) 35:67-76 (2012)
DOI:10.1007/s13402-011-0069-x

Reference

PMID:23731971

Authors

DiMaio D, Petti LM

Title

The E5 proteins.

Journal

Virology 445:99-114 (2013)
DOI:10.1016/j.virol.2013.05.006

Reference

PMID:23403708

Authors

De Marco F

Title

Oxidative stress and HPV carcinogenesis.

Journal

Viruses 5:708-31 (2013)
DOI:10.3390/v5020708

Reference

PMID:26643553

Authors

Wieringa HW, van der Zee AG, de Vries EG, van Vugt MA

Title

Breaking the DNA damage response to improve cervical cancer treatment.

Journal

Cancer Treat Rev 42:30-40 (2016)
DOI:10.1016/j.ctrv.2015.11.008

Reference

PMID:19861444

Authors

Chung CH, Gillison ML

Title

Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications.

Journal

Clin Cancer Res 15:6758-62 (2009)
DOI:10.1158/1078-0432.CCR-09-0784

Reference

PMID:11325599

Authors

Koromilas AE, Li S, Matlashewski G

Title

Control of interferon signaling in human papillomavirus infection.

Journal

Cytokine Growth Factor Rev 12:157-70 (2001)
DOI:10.1016/S1359-6101(00)00023-X

Reference

PMID:10702232

Authors

Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ

Title

Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis.

Journal

J Biol Chem 275:6764-9 (2000)
DOI:10.1074/jbc.275.10.6764

Reference

PMID:22499770

Authors

Sandberg A, Lindell G, Kallstrom BN, Branca RM, Danielsson KG, Dahlberg M, Larson B, Forshed J, Lehtio J

Title

Tumor proteomics by multivariate analysis on individual pathway data for characterization of vulvar cancer phenotypes.

Journal

Mol Cell Proteomics 11:M112.016998 (2012)
DOI:10.1074/mcp.M112.016998

Reference

PMID:9990017