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aml05166                    Pathway                                

HTLV-I infection - Ailuropoda melanoleuca (giant panda)
Human T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Expression of Tax, a viral regulatory protein is critical to the pathogenesis. Tax is a transcriptional co-factor that interfere several signaling pathways related to anti-apoptosis or cell proliferation. The modulation of the signaling by Tax involve its binding to transcription factors like CREB/ATF, NF-kappa B, SRF, and NFAT.
Human Diseases; Infectious diseases
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HTLV-I infection

All organismsOrtholog table
Ailuropoda melanoleuca (giant panda) [GN:aml]
TGFB1; transforming growth factor beta 1 [KO:K13375]
TGFB2; transforming growth factor beta 2 [KO:K13376]
TGFB3; transforming growth factor beta 3 [KO:K13377]
SLC2A1; solute carrier family 2 member 1 [KO:K07299]
NRP1; neuropilin 1 [KO:K06724]
VCAM1; vascular cell adhesion molecule 1 [KO:K06527]
CD3D; CD3d molecule [KO:K06450]
CD3E; CD3e molecule [KO:K06451]
CD3G; CD3g molecule [KO:K06452]
ICAM1; intercellular adhesion molecule 1 [KO:K06490]
ITGAL; integrin subunit alpha L [KO:K05718]
ITGB2; integrin subunit beta 2 [KO:K06464]
TLN1; talin 1 [KO:K06271]
TLN2; talin 2 [KO:K06271]
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
TRRAP; transformation/transcription domain associated protein [KO:K08874]
KAT5; lysine acetyltransferase 5 [KO:K11304] [EC:]
CCND2; cyclin D2 [KO:K10151]
RANBP3L; RAN binding protein 3 like [KO:K15304]
RANBP3; RAN binding protein 3 [KO:K15304]
RAN; RAN, member RAS oncogene family [KO:K07936]
XPO1; exportin 1 [KO:K14290]
class I histocompatibility antigen, Aime-1906 [KO:K06751]
AIME-152; class I histocompatibility antigen, Aime-152 [KO:K06751]
H-2 class I histocompatibility antigen, Q10 alpha chain [KO:K06751]
CALR; calreticulin [KO:K08057]
PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:]
PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:]
PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:]
PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
CANX; calnexin [KO:K08054]
IL2RB; interleukin 2 receptor subunit beta [KO:K05069]
IL2RG; interleukin 2 receptor subunit gamma [KO:K05070]
JAK1; Janus kinase 1 [KO:K11217] [EC:]
JAK3; Janus kinase 3 [KO:K11218] [EC:]
STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
FDPS; farnesyl diphosphate synthase [KO:K00787] [EC:]
HRAS; HRas proto-oncogene, GTPase [KO:K02833]
KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07829]
RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
MRAS; muscle RAS oncogene homolog [KO:K07831]
VDAC1; voltage dependent anion channel 1 [KO:K05862]
SLC25A4; solute carrier family 25 member 4 [KO:K05863]
SLC25A31; solute carrier family 25 member 31 [KO:K05863]
SLC25A6; solute carrier family 25 member 6 [KO:K05863]
SLC25A5; solute carrier family 25 member 5 [KO:K05863]
VDAC2; voltage dependent anion channel 2 [KO:K15040]
VDAC3; voltage dependent anion channel 3 [KO:K15041]
TSPO; translocator protein [KO:K05770]
VAC14; Vac14, PIKFYVE complex component [KO:K15305]
RANBP1; RAN binding protein 1 [KO:K15306]
MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:]
BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
CDC20; cell division cycle 20 [KO:K03363]
ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
CDC27; cell division cycle 27 [KO:K03350]
ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
CDC16; cell division cycle 16 [KO:K03353]
ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
CDC23; cell division cycle 23 [KO:K03355]
ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
CDC26; cell division cycle 26 [KO:K03359]
PTTG1; pituitary tumor-transforming 1 [KO:K06635]
CCNB2; cyclin B2 [KO:K21770]
CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
PCNA; proliferating cell nuclear antigen [KO:K04802]
POLD1; DNA polymerase delta 1, catalytic subunit [KO:K02327] [EC:]
POLD2; DNA polymerase delta 2, accessory subunit [KO:K02328]
POLD3; DNA polymerase delta 3, accessory subunit [KO:K03504]
POLD4; DNA polymerase delta 4, accessory subunit [KO:K03505]
POLE; DNA polymerase epsilon, catalytic subunit [KO:K02324] [EC:]
POLE2; DNA polymerase epsilon 2, accessory subunit [KO:K02325] [EC:]
POLE3; DNA polymerase epsilon 3, accessory subunit [KO:K02326] [EC:]
POLE4; DNA polymerase epsilon 4, accessory subunit [KO:K03506] [EC:]
CCND1; cyclin D1 [KO:K04503]
CCND3; cyclin D3 [KO:K10152]
CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:]
RB1; RB transcriptional corepressor 1 [KO:K06618]
E2F2; E2F transcription factor 2 [KO:K09389]
E2F3; E2F transcription factor 3 [KO:K06620]
CDKN2A; cyclin dependent kinase inhibitor 2A [KO:K06621]
CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
WNT1; Wnt family member 1 [KO:K03209]
WNT2; Wnt family member 2 [KO:K00182]
WNT2B; Wnt family member 2B [KO:K00182]
WNT3; Wnt family member 3 [KO:K00312]
WNT3A; Wnt family member 3A [KO:K00312]
WNT4; Wnt family member 4 [KO:K00408]
WNT5A; Wnt family member 5A [KO:K00444]
WNT5B; Wnt family member 5B [KO:K00444]
WNT6; Wnt family member 6 [KO:K00445]
WNT7A; Wnt family member 7A [KO:K00572]
WNT7B; Wnt family member 7B [KO:K00572]
WNT8B; Wnt family member 8B [KO:K00714]
WNT8A; Wnt family member 8A [KO:K00714]
WNT9B; Wnt family member 9B [KO:K01064]
WNT9A; Wnt family member 9A [KO:K01064]
WNT10A; Wnt family member 10A [KO:K01357]
WNT10B; Wnt family member 10B [KO:K01357]
WNT11; Wnt family member 11 [KO:K01384]
WNT16; Wnt family member 16 [KO:K01558]
FZD1; frizzled class receptor 1 [KO:K02432]
FZD7; frizzled class receptor 7 [KO:K02432]
FZD2; frizzled class receptor 2 [KO:K02235]
FZD3; frizzled class receptor 3 [KO:K02329]
FZD4; frizzled class receptor 4 [KO:K02354]
FZD5; frizzled class receptor 5 [KO:K02375]
FZD8; frizzled class receptor 8 [KO:K02375]
FZD6; frizzled class receptor 6 [KO:K02376]
FZD10; frizzled class receptor 10 [KO:K02842]
FZD9; frizzled class receptor 9 [KO:K02842]
DVL3; dishevelled segment polarity protein 3 [KO:K02353]
DVL1; dishevelled segment polarity protein 1 [KO:K02353]
DVL2; dishevelled segment polarity protein 2 [KO:K02353]
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
CTNNB1; catenin beta 1 [KO:K02105]
APC; APC, WNT signaling pathway regulator [KO:K02085]
APC2; APC2, WNT signaling pathway regulator [KO:K02085]
DLG1; discs large MAGUK scaffold protein 1 [KO:K12076]
PDGFA; platelet derived growth factor subunit A [KO:K04359]
PDGFB; platelet derived growth factor subunit B [KO:K17386]
PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:]
PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:]
PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
TNF; tumor necrosis factor [KO:K03156]
TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:]
MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:]
JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
GPS2; G protein pathway suppressor 2 [KO:K15307]
IL1R1; interleukin 1 receptor type 1 [KO:K04386]
IL1R2; interleukin 1 receptor type 2 [KO:K04387]
T-cell receptor alpha chain V region CTL-F3 [KO:K10784]
MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:]
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:]
IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
NFKBIA; NFKB inhibitor alpha [KO:K04734]
NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
LTBR; lymphotoxin beta receptor [KO:K03159]
CD40; CD40 molecule [KO:K03160]
TNFRSF13C; TNF receptor superfamily member 13C [KO:K05151]
MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253]
NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
IL2; interleukin 2 [KO:K05429]
IL2RA; interleukin 2 receptor subunit alpha [KO:K05068]
IL15; interleukin 15 [KO:K05433]
IL15RA; interleukin 15 receptor subunit alpha [KO:K05074]
IL6; interleukin 6 [KO:K05405]
uncharacterized LOC100473502 [KO:K05427]
CSF2; colony stimulating factor 2 [KO:K05427]
LTA; lymphotoxin alpha [KO:K05468]
BCL2L1; BCL2 like 1 [KO:K04570]
XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:]
ZFP36; ZFP36 ring finger protein [KO:K15308]
NFYB; nuclear transcription factor Y subunit beta [KO:K08065]
HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
HLA-DMA; HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
HLA-DMB; HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
HLA-DOB; HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
Aime-DQB; HLA class II histocompatibility antigen, DQ beta 2 chain [KO:K06752]
Aime-DQA; SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
Aime-DRB1; DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
Aime-DRA; HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
SRF; serum response factor [KO:K04378]
ELK4; ELK4, ETS transcription factor [KO:K04376]
ELK1; ELK1, ETS transcription factor [KO:K04375]
SPI1; Spi-1 proto-oncogene [KO:K09438]
ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678]
ETS2; ETS proto-oncogene 2, transcription factor [KO:K21932]
TBPL1; TATA-box binding protein like 1 [KO:K03120]
TBP; TATA-box binding protein [KO:K03120]
TATA box-binding protein-like protein 2 [KO:K03120]
FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
EGR1; early growth response 1 [KO:K09203]
EGR2; early growth response 2 [KO:K12496]
FOSL1; FOS like 1, AP-1 transcription factor subunit [KO:K04502]
ADCY1; adenylate cyclase 1 [KO:K08041] [EC:]
ADCY2; adenylate cyclase 2 [KO:K08042] [EC:]
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:]
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:]
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:]
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:]
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:]
ADCY8; adenylate cyclase 8 [KO:K08048] [EC:]
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:]
PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:]
PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:]
CREB1; cAMP responsive element binding protein 1 [KO:K05870]
CREM; cAMP responsive element modulator [KO:K09052]
ATF1; activating transcription factor 1 [KO:K09053]
ATF2; activating transcription factor 2 [KO:K04450]
ATF3; activating transcription factor 3 [KO:K09032]
ATF4; activating transcription factor 4 [KO:K04374]
XBP1; X-box binding protein 1 [KO:K09027]
CRTC1; CREB regulated transcription coactivator 1 [KO:K15309]
CRTC2; CREB regulated transcription coactivator 2 [KO:K16333]
CRTC3; CREB regulated transcription coactivator 3 [KO:K16334]
CREBBP; CREB binding protein [KO:K04498] [EC:]
EP300; E1A binding protein p300 [KO:K04498] [EC:]
KAT2B; lysine acetyltransferase 2B [KO:K06062] [EC:]
KAT2A; lysine acetyltransferase 2A [KO:K06062] [EC:]
TCF3; transcription factor 3 [KO:K09063]
POLB; DNA polymerase beta [KO:K02330] [EC:4.2.99.-]
CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:]
TERT; telomerase reverse transcriptase [KO:K11126] [EC:]
MYB; MYB proto-oncogene, transcription factor [KO:K09420]
MYBL2; MYB proto-oncogene like 2 [KO:K21769]
TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:]
TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:]
SMAD3; SMAD family member 3 [KO:K04500]
SMAD2; SMAD family member 2 [KO:K04500]
SMAD4; SMAD family member 4 [KO:K04501]
ATM; ATM serine/threonine kinase [KO:K04728] [EC:]
ATR; ATR serine/threonine kinase [KO:K06640] [EC:]
CHEK1; checkpoint kinase 1 [KO:K02216] [EC:]
CHEK2; checkpoint kinase 2 [KO:K06641] [EC:]
TP53; tumor protein p53 [KO:K04451]
BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
TP53INP1; tumor protein p53 inducible nuclear protein 1 [KO:K15310]
MSX2; msh homeobox 2 [KO:K09341]
MSX1; msh homeobox 1 [KO:K09341]
homeobox protein MSX-3-like [KO:K09341]
Hydrogen peroxide
Calcium cation
Potassium cation
3',5'-Cyclic AMP
Accessory protein p12I
P13 protein
Accessory protein p30II
HTLV-1 basic zipper factor
Yoshida M
Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.
Annu Rev Immunol 19:475-96 (2001)
Gatza ML, Watt JC, Marriott SJ
Cellular transformation by the HTLV-I Tax protein, a jack-of-all-trades.
Oncogene 22:5141-9 (2003)
Ghez D, Lepelletier Y, Jones KS, Pique C, Hermine O
Current concepts regarding the HTLV-1 receptor complex.
Retrovirology 7:99 (2010)
Boxus M, Willems L
Mechanisms of HTLV-1 persistence and transformation.
Br J Cancer 101:1497-501 (2009)
Matsuoka M, Jeang KT
Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation.
Nat Rev Cancer 7:270-80 (2007)
Yasunaga J, Matsuoka M
[HTLV-I and leukemogenesis].
Uirusu 56:241-9 (2006)
Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L
The HTLV-1 Tax interactome.
Retrovirology 5:76 (2008)
Harhaj EW, Harhaj NS
Mechanisms of persistent NF-kappaB activation by HTLV-I tax.
IUBMB Life 57:83-91 (2005)
Peloponese JM Jr, Jeang KT
Role for Akt/protein kinase B and activator protein-1 in cellular proliferation induced by the human T-cell leukemia virus type 1 tax oncoprotein.
J Biol Chem 281:8927-38 (2006)
Marriott SJ, Semmes OJ
Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response.
Oncogene 24:5986-95 (2005)
Jeang KT
Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: cellular signaling through NF-kappa B.
Cytokine Growth Factor Rev 12:207-17 (2001)
Bouzar AB, Willems L
How HTLV-1 may subvert miRNAs for persistence and transformation.
Retrovirology 5:101 (2008)
Sun SC, Yamaoka S
Activation of NF-kappaB by HTLV-I and implications for cell transformation.
Oncogene 24:5952-64 (2005)
Manel N, Battini JL, Taylor N, Sitbon M
HTLV-1 tropism and envelope receptor.
Oncogene 24:6016-25 (2005)
Sun SC, Ballard DW
Persistent activation of NF-kappaB by the tax transforming protein of HTLV-1: hijacking cellular IkappaB kinases.
Oncogene 18:6948-58 (1999)
Taylor GP, Matsuoka M
Natural history of adult T-cell leukemia/lymphoma and approaches to therapy.
Oncogene 24:6047-57 (2005)
Franchini G, Fukumoto R, Fullen JR
T-cell control by human T-cell leukemia/lymphoma virus type 1.
Int J Hematol 78:280-96 (2003)
Baydoun HH, Bellon M, Nicot C
HTLV-1 Yin and Yang: Rex and p30 master regulators of viral mRNA trafficking.
AIDS Rev 10:195-204 (2008)
Jin DY, Teramoto H, Giam CZ, Chun RF, Gutkind JS, Jeang KT
A human suppressor of c-Jun N-terminal kinase 1 activation by tumor necrosis factor alpha.
J Biol Chem 272:25816-23 (1997)
Pise-Masison CA, Brady JN
Setting the stage for transformation: HTLV-1 Tax inhibition of p53 function.
Front Biosci 10:919-30 (2005)
KO pathway

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