KEGG   PATHWAY: ko05166Help
ko05166                     Pathway                                

HTLV-I infection
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.
09160 Human Diseases; 09167 Infectious diseases
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Pathway map
ko05166  HTLV-I infection

Ortholog table
H00009  Adult T-cell leukemia
H01724  HTLV1-associated myelopathy (HAM)
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K07299  MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K19259  envelope glycoprotein gp62
K06724  neuropilin 1
K06527  vascular cell adhesion molecule 1
K06450  T-cell surface glycoprotein CD3 delta chain
K06451  T-cell surface glycoprotein CD3 epsilon chain
K06452  T-cell surface glycoprotein CD3 gamma chain
K06490  intercellular adhesion molecule 1
K05718  integrin alpha L
K06464  integrin beta 2
K06271  talin
K04377  Myc proto-oncogene protein
K08874  transformation/transcription domain-associated protein
K11304  histone acetyltransferase HTATIP [EC:]
K10151  G1/S-specific cyclin-D2
K15304  Ran-binding protein 3
K07936  GTP-binding nuclear protein Ran
K14290  exportin-1
K06751  major histocompatibility complex, class I
K08057  calreticulin
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K04446  nuclear factor of activated T-cells, cytoplasmic 1
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K17333  nuclear factor of activated T-cells, cytoplasmic 3
K17334  nuclear factor of activated T-cells, cytoplasmic 4
K08054  calnexin
K05069  interleukin 2 receptor beta
K05070  interleukin 2 receptor gamma
K11217  Janus kinase 1 [EC:]
K11218  Janus kinase 3 [EC:]
K11223  signal transducer and activator of transcription 5A
K11224  signal transducer and activator of transcription 5B
K00787  farnesyl diphosphate synthase [EC:]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K07829  Ras-related protein R-Ras
K07830  Ras-related protein R-Ras2
K07831  Ras-related protein M-Ras
K05862  voltage-dependent anion channel protein 1
K05863  solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K15040  voltage-dependent anion channel protein 2
K15041  voltage-dependent anion channel protein 3
K05770  translocator protein
K15305  vacuole morphology and inheritance protein 14
K15306  Ran-binding protein 1
K06679  mitotic spindle assembly checkpoint protein MAD1
K02537  mitotic spindle assembly checkpoint protein MAD2
K06637  mitotic checkpoint serine/threonine-protein kinase BUB1 beta [EC:]
K02180  cell cycle arrest protein BUB3
K03363  cell division cycle 20, cofactor of APC complex
K03348  anaphase-promoting complex subunit 1
K03349  anaphase-promoting complex subunit 2
K03350  anaphase-promoting complex subunit 3
K03351  anaphase-promoting complex subunit 4
K03352  anaphase-promoting complex subunit 5
K03353  anaphase-promoting complex subunit 6
K03354  anaphase-promoting complex subunit 7
K03355  anaphase-promoting complex subunit 8
K03356  anaphase-promoting complex subunit 9
K03357  anaphase-promoting complex subunit 10
K03358  anaphase-promoting complex subunit 11
K03359  anaphase-promoting complex subunit 12
K12416  anaphase-promoting complex subunit SWM1
K06635  securin
K21770  G2/mitotic-specific cyclin-B2
K06625  cyclin-dependent kinase inhibitor 1A
K04802  proliferating cell nuclear antigen
K02327  DNA polymerase delta subunit 1 [EC:]
K02328  DNA polymerase delta subunit 2
K03504  DNA polymerase delta subunit 3
K03505  DNA polymerase delta subunit 4
K02324  DNA polymerase epsilon subunit 1 [EC:]
K02325  DNA polymerase epsilon subunit 2 [EC:]
K02326  DNA polymerase epsilon subunit 3 [EC:]
K03506  DNA polymerase epsilon subunit 4 [EC:]
K04503  G1/S-specific cyclin-D1
K10152  G1/S-specific cyclin-D3
K02089  cyclin-dependent kinase 4 [EC:]
K06618  retinoblastoma-associated protein
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K06621  cyclin-dependent kinase inhibitor 2A
K04685  cyclin-dependent kinase inhibitor 2B
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
K04690  frizzled
K02353  segment polarity protein dishevelled
K03083  glycogen synthase kinase 3 beta [EC:]
K02105  catenin beta 1
K02085  adenomatosis polyposis coli protein
K12076  disks large protein 1
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K04363  platelet-derived growth factor receptor alpha [EC:]
K05089  platelet-derived growth factor receptor beta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K04456  RAC serine/threonine-protein kinase [EC:]
K03156  tumor necrosis factor superfamily, member 2
K03158  tumor necrosis factor receptor superfamily member 1A
K04416  mitogen-activated protein kinase kinase kinase 1 [EC:]
K04430  mitogen-activated protein kinase kinase 4 [EC:]
K04448  transcription factor AP-1
K15307  G protein pathway suppressor 2
K04386  interleukin 1 receptor type I
K04387  interleukin 1 receptor type II
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K04421  mitogen-activated protein kinase kinase kinase 3 [EC:]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K03159  lymphotoxin beta receptor TNFR superfamily member 3
K03160  tumor necrosis factor receptor superfamily member 5
K05151  tumor necrosis factor receptor superfamily member 13C
K04466  mitogen-activated protein kinase kinase kinase 14 [EC:]
K09253  transcription factor RelB
K04469  nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K05429  interleukin 2
K05068  interleukin 2 receptor alpha
K05433  interleukin 15
K05074  interleukin 15 receptor alpha
K05405  interleukin 6
K05427  granulocyte-macrophage colony-stimulating factor
K05468  lymphotoxin alpha (TNF superfamily, member 1)
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04725  E3 ubiquitin-protein ligase XIAP [EC:]
K15308  tristetraprolin
K08065  nuclear transcription Y subunit beta
K06752  major histocompatibility complex, class II
K04378  serum response factor
K04376  ETS domain-containing protein Elk-4
K04375  ETS domain-containing protein Elk-1
K09438  transcription factor PU.1
K02678  C-ets-1
K21932  C-ets-2
K03120  transcription initiation factor TFIID TATA-box-binding protein
K04379  proto-oncogene protein c-fos
K09203  early growth response protein 1
K12496  early growth response protein 2
K04502  fos-like antigen 1
K08041  adenylate cyclase 1 [EC:]
K08042  adenylate cyclase 2 [EC:]
K08043  adenylate cyclase 3 [EC:]
K08044  adenylate cyclase 4 [EC:]
K08045  adenylate cyclase 5 [EC:]
K08046  adenylate cyclase 6 [EC:]
K08047  adenylate cyclase 7 [EC:]
K08048  adenylate cyclase 8 [EC:]
K08049  adenylate cyclase 9 [EC:]
K04345  protein kinase A [EC:]
K05870  cyclic AMP-responsive element-binding protein 1
K09052  cAMP response element modulator
K09053  activating transcription factor 1
K04450  cyclic AMP-dependent transcription factor ATF-2
K09032  activating transcription factor 3
K04374  cyclic AMP-dependent transcription factor ATF-4
K09027  X box-binding protein 1
K15309  CREB-regulated transcription coactivator 1
K16333  CREB-regulated transcription coactivator 2
K16334  CREB-regulated transcription coactivator 3
K04498  E1A/CREB-binding protein [EC:]
K06062  histone acetyltransferase [EC:]
K09063  transcription factor E2-alpha
K02330  DNA polymerase beta [EC:4.2.99.-]
K06622  cyclin-dependent kinase inhibitor 2C
K05856  lymphocyte cell-specific protein tyrosine kinase [EC:]
K11126  telomerase reverse transcriptase [EC:]
K09420  transcriptional activator Myb
K21769  myb-related protein B
K04674  TGF-beta receptor type-1 [EC:]
K04388  TGF-beta receptor type-2 [EC:]
K04500  mothers against decapentaplegic homolog 2/3
K04501  mothers against decapentaplegic homolog 4
K04728  ataxia telangiectasia mutated family protein [EC:]
K06640  serine/threonine-protein kinase ATR [EC:]
K02216  serine/threonine-protein kinase Chk1 [EC:]
K06641  serine/threonine-protein kinase Chk2 [EC:]
K04451  tumor protein p53
K02159  apoptosis regulator BAX
K15310  tumor protein p53-inducible nuclear protein 1
K09341  homeobox protein MSX
C00027  Hydrogen peroxide
C00076  Calcium cation
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C18994  Accessory protein p12I
C18995  P13 protein
C18996  Accessory protein p30II
C19313  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)
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