KEGG   PATHWAY: umr05203
Entry
umr05203                    Pathway                                
Name
Viral carcinogenesis - Ursus maritimus (polar bear)
Description
There is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Via expression of many potent oncoproteins, these tumor viruses promote an aberrant cell-proliferation via modulating cellular cell-signaling pathways and escape from cellular defense system such as blocking apoptosis. Human tumor virus oncoproteins can also disrupt pathways that are necessary for the maintenance of the integrity of host cellular genome. Viruses that encode such activities can contribute to initiation as well as progression of human cancers.
Class
Human Diseases; Cancer: overview
Pathway map
umr05203  Viral carcinogenesis
umr05203

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103669776  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103669173  LOW QUALITY PROTEIN: GTPase HRas-like [KO:K02833]
103671035  HRAS; GTPase HRas isoform X3 [KO:K02833]
103665244  KRAS; GTPase KRas isoform X1 [KO:K07827]
103669422  NRAS; GTPase NRas [KO:K07828]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103659802  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103659593  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103676372  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103681679  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103668409  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103667087  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
103669052  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
103672393  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103658932  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
103682282  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
103678159  DDB1; DNA damage-binding protein 1 [KO:K10610]
103661509  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
103675032  YWHAQ; 14-3-3 protein theta [KO:K16197]
103669726  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
103681664  14-3-3 protein zeta/delta-like [KO:K16197]
103667175  14-3-3 protein epsilon [KO:K06630]
103681113  YWHAH; 14-3-3 protein eta [KO:K16198]
103670210  YWHAG; 14-3-3 protein gamma [KO:K16198]
103663059  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103672573  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103672571  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
103672570  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
103680991  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
103682491  HPN; serine protease hepsin [KO:K08665] [EC:3.4.21.106]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103679584  RELA; transcription factor p65 [KO:K04735]
103671295  REL; proto-oncogene c-Rel isoform X1 [KO:K09254]
103659023  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103660368  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103661328  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
103661444  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
103682503  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
103667995  E3 SUMO-protein ligase EGR2 [KO:K12496]
121101184  E3 SUMO-protein ligase EGR2-like [KO:K12496]
103673339  EGR3; early growth response protein 3 [KO:K12497]
103677056  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
103656207  LTBR; tumor necrosis factor receptor superfamily member 3 isoform X1 [KO:K03159]
103662689  SP100; nuclear autoantigen Sp-100 isoform X1 [KO:K15413]
103667628  HNRNPK; heterogeneous nuclear ribonucleoprotein K isoform X1 [KO:K12886]
103665536  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103679209  DDX3X; ATP-dependent RNA helicase DDX3X isoform X1 [KO:K11594] [EC:5.6.2.7]
103680200  ATP-dependent RNA helicase DDX3X isoform X1 [KO:K11594] [EC:5.6.2.7]
103671577  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
103662972  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103682183  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103675458  LOW QUALITY PROTEIN: histone H2B-like [KO:K11252]
103660949  histone H2B type 2-E1 [KO:K11252]
103678852  histone H2B type 3-B [KO:K11252]
103678853  histone H2B type 3-B-like [KO:K11252]
103663868  histone H2B subacrosomal variant-like [KO:K11252]
103665033  histone H2B type 1-A [KO:K11252]
103665034  histone H2B type 1-A [KO:K11252]
103665041  histone H2B type 1-B-like isoform X1 [KO:K11252]
103665047  histone H2B type 1-C/E/F/G/I [KO:K11252]
103665052  histone H2B type 1-M [KO:K11252]
103665053  histone H2B type 1-C/E/F/G/I isoform X1 [KO:K11252]
103665055  histone H2B type 1-L [KO:K11252]
103665059  histone H2B type 2-E-like isoform X1 [KO:K11252]
103665065  histone H2B type 1-K-like [KO:K11252]
103665066  histone H2B type 1-K [KO:K11252]
103665070  histone H2B type 1-C/E/F/G/I [KO:K11252]
103665072  histone H2B type 1-C/E/F/G/I [KO:K11252]
103665081  histone H2B type 1-K-like [KO:K11252]
103665086  histone H2B type 1-J [KO:K11252]
103665098  histone H2B type 1-C/E/F/G/I [KO:K11252]
103665100  histone H2B type 1-N [KO:K11252]
103665103  histone H2B type 1-C/E/F/G/I isoform X1 [KO:K11252]
103667572  histone H2B type 2-E [KO:K11252]
103667575  histone H2B type 2-E [KO:K11252]
103667578  histone H2B type 2-F-like isoform X1 [KO:K11252]
103665194  histone H2B type 1-N-like [KO:K11252]
121102015  histone H2B type 2-E [KO:K11252]
121102419  late histone H2B.L4-like [KO:K11252]
121102568  late histone H2B.L4-like [KO:K11252]
103682263  histone H4-like [KO:K11254]
103677773  histone H4 [KO:K11254]
103665044  histone H4 [KO:K11254]
103665050  histone H4-like [KO:K11254]
103665054  histone H4 [KO:K11254]
103665083  histone H4 [KO:K11254]
103667579  histone H4 [KO:K11254]
103657107  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
103665736  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103673673  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
103667741  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103673156  TBPL2; TATA box-binding protein-like 2 [KO:K03120]
103660778  TATA-box-binding protein [KO:K03120]
103663386  TBPL1; TATA box-binding protein-like 1 [KO:K03120]
103668586  USP7; ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
103656869  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
103658384  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
103669875  RBPJL; recombining binding protein suppressor of hairless-like protein isoform X1 [KO:K06053]
103670735  SNW1; SNW domain-containing protein 1 [KO:K06063]
103659412  GTF2H1; general transcription factor IIH subunit 1 isoform X1 [KO:K03141]
103663603  GTF2H2C; general transcription factor IIH subunit 2-like protein [KO:K03142]
103661127  GTF2H3; general transcription factor IIH subunit 3 isoform X2 [KO:K03143]
103665011  GTF2H4; general transcription factor IIH subunit 4 isoform X2 [KO:K03144]
103678836  GTF2E1; general transcription factor IIE subunit 1 [KO:K03136]
103659085  GTF2E2; transcription initiation factor IIE subunit beta [KO:K03137]
103676629  SND1; staphylococcal nuclease domain-containing protein 1 [KO:K15979]
103668810  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
103674159  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103662925  GTF2B; transcription initiation factor IIB [KO:K03124]
103671139  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103675743  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103664092  CCND3; G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
103658796  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103661798  CCNA2; cyclin-A2 [KO:K06627]
103664372  CCNA1; cyclin-A1 [KO:K06627]
103664708  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
103664995  MRPS18B; 28S ribosomal protein S18b, mitochondrial [KO:K16174]
103670373  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
103675245  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
103656774  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
103672476  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
103675167  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
103677438  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
103663192  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
103661399  ATP6V0D2; V-type proton ATPase subunit d 2 [KO:K02146]
103673659  ATP6V0D1; V-type proton ATPase subunit d 1 [KO:K02146]
103677080  UBE3A; ubiquitin-protein ligase E3A isoform X1 [KO:K10587] [EC:2.3.2.26]
103678920  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
103656708  protein scribble homolog isoform X1 [KO:K16175]
103678355  PXN; paxillin isoform X1 [KO:K05760]
103665481  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
103657131  IRF3; interferon regulatory factor 3 [KO:K05411]
103670329  PSMC1; 26S proteasome regulatory subunit 4 [KO:K03062]
103677688  RB1; retinoblastoma-associated protein [KO:K06618]
103669778  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103673796  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
103677760  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
103666606  UBR4; E3 ubiquitin-protein ligase UBR4 [KO:K10691] [EC:2.3.2.27]
103670861  JUN; transcription factor AP-1 [KO:K04448]
103656196  CHD4; chromodomain-helicase-DNA-binding protein 4 isoform X1 [KO:K11643] [EC:5.6.2.-]
103676974  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103666443  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103663723  HDAC3; histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
103662823  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
103665860  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
103668837  HDAC6; LOW QUALITY PROTEIN: histone deacetylase 6 [KO:K11407] [EC:3.5.1.98]
103675597  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
103680190  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
103658850  HDAC9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
103674006  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
103669506  HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
103679016  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
103679279  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
103668813  DNAJA3; dnaJ homolog subfamily A member 3, mitochondrial isoform X1 [KO:K09504]
103681930  KAT2B; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
103672619  KAT2A; histone acetyltransferase KAT2A isoform X1 [KO:K06062] [EC:2.3.1.48]
103670603  GTF2A1; transcription initiation factor IIA subunit 1 [KO:K03122]
103671249  GTF2A1L; TFIIA-alpha and beta-like factor isoform X1 [KO:K03122]
103676803  GTF2A2; transcription initiation factor IIA subunit 2 [KO:K03123]
103664154  SRF; serum response factor [KO:K04378]
103679680  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103681607  RASA2; ras GTPase-activating protein 2 isoform X1 [KO:K08053]
103666578  CDC42; cell division control protein 42 homolog [KO:K04393]
103670095  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103674825  RHOA; transforming protein RhoA [KO:K04513]
103659029  SCIN; adseverin [KO:K05768]
103670367  GSN; gelsolin isoform X2 [KO:K05768]
103661071  ACTN4; alpha-actinin-4 [KO:K05699]
103674291  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
103656694  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103666989  cyclin-dependent kinase 4 inhibitor B-like isoform X1 [KO:K06621]
103679831  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
103660629  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
103670813  CDC20; cell division cycle protein 20 homolog [KO:K03363]
103670064  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
103673698  VAC14; protein VAC14 homolog [KO:K15305]
103669262  RANBP1; ran-specific GTPase-activating protein isoform X1 [KO:K15306]
103677058  POLB; DNA polymerase beta isoform X1 [KO:K02330] [EC:2.7.7.7 4.2.99.-]
103671092  IRF7; LOW QUALITY PROTEIN: interferon regulatory factor 7 [KO:K09447]
103663669  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
103674885  CCR5; C-C chemokine receptor type 5 [KO:K04180]
103680537  CCR8; C-C chemokine receptor type 8 [KO:K04183]
103674890  C-C chemokine receptor type 3 isoform X2 [KO:K04178]
103680999  CCR4; C-C chemokine receptor type 4 [KO:K04179]
103657756  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103659742  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
103679423  BAD; bcl2-associated agonist of cell death [KO:K02158]
103676254  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
103681871  C3; complement C3 [KO:K03990]
103680441  DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751]
103656357  H-2 class I histocompatibility antigen, Q10 alpha chain [KO:K06751]
103680561  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
103672268  class I histocompatibility antigen, Gogo-OKO alpha chain [KO:K06751]
103682344  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
121104340  LOW QUALITY PROTEIN: DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
Reference
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  Authors
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  Title
Viruses associated with human cancer.
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Nat Rev Cancer 10:878-89 (2010)
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APMIS 117:382-99 (2009)
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Cancer Biol Ther 10:961-78 (2010)
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Oncogene 27 Suppl 2:S31-42 (2008)
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PMID:16459163
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Effects of hepatitis B virus X protein on the development of liver cancer.
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PMID:12686421
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Hepatitis viruses and the MAPK pathway: is this a survival strategy?
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Virus Res 92:131-40 (2003)
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J Gastroenterol 46:974-90 (2011)
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  Title
Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.
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Adv Cancer Res 103:75-109 (2009)
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  Title
Viral hepatocarcinogenesis: from infection to cancer.
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Liver Int 28:175-88 (2008)
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Reference
PMID:9343405
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Activation of Src family kinases by hepatitis B virus HBx protein and coupled signaling to Ras.
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Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin.
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Mol Cell 19:159-70 (2005)
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Viruses 1:630-46 (2009)
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Reference
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  Title
X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway.
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J Biol Chem 276:8328-40 (2001)
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PMID:10824878
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Arbuthnot P, Capovilla A, Kew M
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J Gastroenterol Hepatol 15:357-68 (2000)
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PMID:9837909
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  Title
The hepatitis B virus HBx protein inhibits caspase 3 activity.
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Schulz TF, Moore PS
  Title
Kaposi's sarcoma-associated herpesvirus: a new human tumor virus, but how?
  Journal
Trends Microbiol 7:196-200 (1999)
DOI:10.1016/S0966-842X(99)01495-X
Reference
PMID:10855768
  Authors
Schulz TF
  Title
Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8): epidemiology and pathogenesis.
  Journal
J Antimicrob Chemother 45 Suppl T3:15-27 (2000)
DOI:10.1093/jac/45.suppl_4.15
Reference
PMID:9594662
  Authors
Moore PS, Chang Y
  Title
Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV.
  Journal
Trends Genet 14:144-50 (1998)
DOI:10.1016/S0168-9525(98)01408-5
Reference
PMID:20534855
  Authors
Pietrek M, Brinkmann MM, Glowacka I, Enlund A, Havemeier A, Dittrich-Breiholz O, Kracht M, Lewitzky M, Saksela K, Feller SM, Schulz TF
  Title
Role of the Kaposi's sarcoma-associated herpesvirus K15 SH3 binding site in inflammatory signaling and B-cell activation.
  Journal
J Virol 84:8231-40 (2010)
DOI:10.1128/JVI.01696-09
Reference
PMID:21421561
  Authors
Bagneris C, Briggs LC, Savva R, Ebrahimi B, Barrett TE
  Title
Crystal structure of a KSHV-SOX-DNA complex: insights into the molecular mechanisms underlying DNase activity and host shutoff.
  Journal
Nucleic Acids Res 39:5744-56 (2011)
DOI:10.1093/nar/gkr111
Reference
PMID:15919895
  Authors
Glaunsinger B, Chavez L, Ganem D
  Title
The exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable.
  Journal
J Virol 79:7396-401 (2005)
DOI:10.1128/JVI.79.12.7396-7401.2005
Related
pathway
umr03022  Basal transcription factors
umr03320  PPAR signaling pathway
umr04010  MAPK signaling pathway
umr04062  Chemokine signaling pathway
umr04064  NF-kappa B signaling pathway
umr04110  Cell cycle
umr04115  p53 signaling pathway
umr04142  Lysosome
umr04151  PI3K-Akt signaling pathway
umr04210  Apoptosis
umr04630  JAK-STAT signaling pathway
umr04662  B cell receptor signaling pathway
umr04810  Regulation of actin cytoskeleton
umr05160  Hepatitis C
umr05161  Hepatitis B
umr05165  Human papillomavirus infection
umr05166  Human T-cell leukemia virus 1 infection
umr05167  Kaposi sarcoma-associated herpesvirus infection
umr05169  Epstein-Barr virus infection
KO pathway
ko05203   
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