Entry
Name
Human papillomavirus infection - Ursus arctos horribilis (North American brown bear)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Ursus arctos horribilis (North American brown bear) [GN:
uah ]
Gene
113254396 DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353 ]
113270636 DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353 ]
113271107 DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353 ]
113257053 MAGI1; membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 isoform X1 [KO:K05631 ]
113252374 PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093 ]
113268543 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
113271290 LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094 ]
113244628 LLGL2; lethal(2) giant larvae protein homolog 2 isoform X1 [KO:K06094 ]
113257484 COL2A1; LOW QUALITY PROTEIN: collagen alpha-1(II) chain [KO:K19719 ]
113258151 COL9A3; LOW QUALITY PROTEIN: collagen alpha-3(IX) chain [KO:K08131 ]
113257988 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
113252355 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
113262825 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
113258968 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
113244663 SLC9A3R1; Na(+)/H(+) exchange regulatory cofactor NHE-RF1 [KO:K13365 ]
113261737 PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382 ] [EC:3.1.3.16 ]
113260072 PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456 ]
113247257 PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456 ]
113269966 PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354 ]
113252071 PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354 ]
113255341 PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354 ]
113266692 PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354 ]
113240812 serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583 ]
113266124 PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583 ]
113253964 PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583 ]
113250050 serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583 ]
113250051 serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583 ]
113262671 PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584 ]
113246276 serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584 ]
113244148 PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584 ]
113261281 PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584 ]
113246356 serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584 ]
113267251 PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584 ]
113262099 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
113254799 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
113270537 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113253989 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113256705 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
113254730 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
113255266 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
113263101 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
113257972 CHD4; LOW QUALITY PROTEIN: chromodomain-helicase-DNA-binding protein 4 [KO:K11643 ] [EC:5.6.2.-]
113249452 HLA class I histocompatibility antigen, A-11 alpha chain-like isoform X1 [KO:K06751 ]
113250163 saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751 ]
113264228 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, A-3 alpha chain [KO:K06751 ]
113243704 DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751 ]
113243706 HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751 ]
113243878 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, A-32 alpha chain-like [KO:K06751 ]
113261534 H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751 ]
113270020 ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147 ]
113244182 ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147 ]
113252853 ATP6V1C1; V-type proton ATPase subunit C 1 isoform X1 [KO:K02148 ]
113269864 ATP6V1C2; V-type proton ATPase subunit C 2 isoform X1 [KO:K02148 ]
113243710 ATP6V1G2; V-type proton ATPase subunit G 2 isoform X1 [KO:K02152 ]
113265420 ATP6V0A1; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154 ]
113264783 ATP6V0A4; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154 ]
113252979 ATP6V0D2; V-type proton ATPase subunit d 2 isoform X1 [KO:K02146 ]
113245138 ATP6V0C; V-type proton ATPase 16 kDa proteolipid subunit [KO:K02155 ]
113254775 ATP6V0B; V-type proton ATPase 21 kDa proteolipid subunit isoform X1 [KO:K03661 ]
113255562 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
113258768 LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632 ]
113250525 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
113264990 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
113264732 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
113245324 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
113260470 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
113242823 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
113262153 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
113250654 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
113256419 STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221 ]
113245987 IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693 ]
113248714 NOTCH3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995 ]
113243767 NOTCH4; neurogenic locus notch homolog protein 4 isoform X1 [KO:K20996 ]
113258648 RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053 ]
113266766 RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053 ]
113268247 HEYL; hairy/enhancer-of-split related with YRPW motif-like protein isoform X1 [KO:K09091 ]
113253020 HEY1; hairy/enhancer-of-split related with YRPW motif protein 1 [KO:K09091 ]
113259415 HEY2; hairy/enhancer-of-split related with YRPW motif protein 2 isoform X1 [KO:K09091 ]
Compound
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Moody CA, Laimins LA
Title
Human papillomavirus oncoproteins: pathways to transformation.
Journal
Reference
Authors
Chen J
Title
Signaling pathways in HPV-associated cancers and therapeutic implications.
Journal
Reference
Authors
Tummers B, Burg SH
Title
High-risk human papillomavirus targets crossroads in immune signaling.
Journal
Reference
Authors
Lehoux M, D'Abramo CM, Archambault J
Title
Molecular mechanisms of human papillomavirus-induced carcinogenesis.
Journal
Reference
Authors
Pang CL, Thierry F
Title
Human papillomavirus proteins as prospective therapeutic targets.
Journal
Reference
Authors
Yugawa T, Kiyono T
Title
Molecular mechanisms of cervical carcinogenesis by high-risk human papillomaviruses: novel functions of E6 and E7 oncoproteins.
Journal
Reference
Authors
Narisawa-Saito M, Kiyono T
Title
Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins.
Journal
Reference
Authors
Wolf JK, Ramirez PT.
Title
The molecular biology of cervical cancer.
Journal
Reference
Authors
zur Hausen H
Title
Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis.
Journal
Reference
Authors
Kim YT, Zhao M
Title
Aberrant cell cycle regulation in cervical carcinoma.
Journal
Reference
Authors
McCance DJ
Title
Human papillomaviruses and cell signaling.
Journal
Reference
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
Authors
Tommasino M
Title
The human papillomavirus family and its role in carcinogenesis.
Journal
Reference
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
Reference
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
Reference
Authors
James CD, Roberts S
Title
Viral Interactions with PDZ Domain-Containing Proteins-An Oncogenic Trait?
Journal
Reference
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
Reference
Authors
Subbaiah VK, Kranjec C, Thomas M, Banks L
Title
PDZ domains: the building blocks regulating tumorigenesis.
Journal
Reference
Authors
Banks L, Pim D, Thomas M
Title
Human tumour viruses and the deregulation of cell polarity in cancer.
Journal
Reference
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
Reference
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
Authors
Garnett TO, Duerksen-Hughes PJ
Title
Modulation of apoptosis by human papillomavirus (HPV) oncoproteins.
Journal
Reference
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
Reference
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
Reference
Authors
DiMaio D, Mattoon D
Title
Mechanisms of cell transformation by papillomavirus E5 proteins.
Journal
Reference
Authors
Ganguly N
Title
Human papillomavirus-16 E5 protein: oncogenic role and therapeutic value.
Journal
Reference
Authors
DiMaio D, Petti LM
Title
The E5 proteins.
Journal
Reference
Authors
De Marco F
Title
Oxidative stress and HPV carcinogenesis.
Journal
Reference
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
Reference
Authors
Chung CH, Gillison ML
Title
Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications.
Journal
Reference
Authors
Koromilas AE, Li S, Matlashewski G
Title
Control of interferon signaling in human papillomavirus infection.
Journal
Reference
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
Reference
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
Reference
Authors
Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, Jansen-Durr P
Title
Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein.
Journal
Reference
Authors
Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y
Title
Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin.
Journal
Reference
Authors
Xu M, Luo W, Elzi DJ, Grandori C, Galloway DA
Title
NFX1 interacts with mSin3A/histone deacetylase to repress hTERT transcription in keratinocytes.
Journal
Reference
Authors
Raff AB, Woodham AW, Raff LM, Skeate JG, Yan L, Da Silva DM, Schelhaas M, Kast WM
Title
The evolving field of human papillomavirus receptor research: a review of binding and entry.
Journal
Related pathway
uah04612 Antigen processing and presentation
uah04620 Toll-like receptor signaling pathway
KO pathway
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