KEGG PATHWAY: map05165

PATHWAY: map05165

Entry

map05165                    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

map05165

Human papillomavirus infection

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