KEGG   PATHWAY: ko05166Help
Entry
ko05166                     Pathway                                

Name
Human T-cell leukemia virus 1 infection
Description
Human T-cell leukemia 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, and SRF.
Class
Human Diseases; Infectious diseases: Viral
BRITE hierarchy
Pathway map
ko05166  Human T-cell leukemia virus 1 infection
ko05166

Ortholog table
Disease
H00009  Adult T-cell leukemia
H01724  HTLV1-associated myelopathy
Orthology
K19259  envelope glycoprotein gp62
K07299  MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K06724  neuropilin 1
K04377  Myc proto-oncogene protein
K08874  transformation/transcription domain-associated protein
K11304  histone acetyltransferase HTATIP [EC:2.3.1.48]
K10151  G1/S-specific cyclin-D2
K05718  integrin alpha L
K06464  integrin beta 2
K06490  intercellular adhesion molecule 1
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K06454  T-cell surface glycoprotein CD4
K23017  HTLV-1 gag polyprotein
K06271  talin
K23018  HTLV-1 rex polyprotein
K15304  Ran-binding protein 3
K07936  GTP-binding nuclear protein Ran
K14290  exportin-1
K08057  calreticulin
K08054  calnexin
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
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
K05069  interleukin 2 receptor beta
K05070  interleukin 2 receptor gamma
K11217  Janus kinase 1 [EC:2.7.10.2]
K11218  Janus kinase 3 [EC:2.7.10.2]
K11223  signal transducer and activator of transcription 5A
K11224  signal transducer and activator of transcription 5B
K05429  interleukin 2
K06751  major histocompatibility complex, class I
K08055  beta-2-microglobulin
K00787  farnesyl diphosphate synthase [EC:2.5.1.10 2.5.1.1]
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
K21857  protein Tax-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:2.7.11.1]
K02180  cell cycle arrest protein BUB3
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
K03357  anaphase-promoting complex subunit 10
K03358  anaphase-promoting complex subunit 11
K03359  anaphase-promoting complex subunit 12
K03363  cell division cycle 20, cofactor of APC complex
K06635  securin
K02365  separase [EC:3.4.22.49]
K21770  G2/mitotic-specific cyclin-B2
K04685  cyclin-dependent kinase inhibitor 2B
K06621  cyclin-dependent kinase inhibitor 2A
K02089  cyclin-dependent kinase 4 [EC:2.7.11.22]
K04503  G1/S-specific cyclin-D1
K10152  G1/S-specific cyclin-D3
K06625  cyclin-dependent kinase inhibitor 1A
K06627  cyclin-A
K06626  G1/S-specific cyclin-E1
K02206  cyclin-dependent kinase 2 [EC:2.7.11.22]
K06618  retinoblastoma-associated protein
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K04728  serine-protein kinase ATM [EC:2.7.11.1]
K06640  serine/threonine-protein kinase ATR [EC:2.7.11.1]
K02216  serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K06641  serine/threonine-protein kinase CHEK2 [EC:2.7.11.1]
K04451  tumor protein p53
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K12076  disks large protein 1
K01110  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.67 3.1.3.48 3.1.3.16]
K03156  tumor necrosis factor superfamily, member 2
K03158  tumor necrosis factor receptor superfamily member 1A
K04416  mitogen-activated protein kinase kinase kinase 1 [EC:2.7.11.25]
K04430  mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04448  transcription factor AP-1
K01397  matrix metalloproteinase-7 (matrilysin, uterine) [EC:3.4.24.23]
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
K06450  T-cell surface glycoprotein CD3 delta chain
K06451  T-cell surface glycoprotein CD3 epsilon chain
K06452  T-cell surface glycoprotein CD3 gamma chain
K04421  mitogen-activated protein kinase kinase kinase 3 [EC:2.7.11.25]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
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
K15307  G protein pathway suppressor 2
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:2.7.11.25]
K09253  transcription factor RelB
K04469  nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K15308  tristetraprolin
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:2.3.2.27]
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K04674  TGF-beta receptor type-1 [EC:2.7.11.30]
K04388  TGF-beta receptor type-2 [EC:2.7.11.30]
K04500  mothers against decapentaplegic homolog 2/3
K04501  mothers against decapentaplegic homolog 4
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
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
K04502  fos-like antigen 1
K12496  early growth response protein 2
K05870  cyclic AMP-responsive element-binding protein 1
K09048  cyclic AMP-responsive element-binding protein 3
K04450  cyclic AMP-dependent transcription factor ATF-2
K04374  cyclic AMP-dependent transcription factor ATF-4
K09047  cyclic AMP-responsive element-binding protein 5
K09049  cyclic AMP-dependent transcription factor ATF-6 beta
K15309  CREB-regulated transcription coactivator 1
K16333  CREB-regulated transcription coactivator 2
K16334  CREB-regulated transcription coactivator 3
K04498  E1A/CREB-binding protein [EC:2.3.1.48]
K06062  histone acetyltransferase [EC:2.3.1.48]
K09063  transcription factor E2-alpha
K02330  DNA polymerase beta [EC:4.2.99.- 2.7.7.7]
K05856  lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2]
K02159  apoptosis regulator BAX
K06622  cyclin-dependent kinase inhibitor 2C
K11126  telomerase reverse transcriptase [EC:2.7.7.49]
K09341  homeobox protein MSX
Compound
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
Reference
  Authors
Matsuoka M, Jeang KT
  Title
Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation.
  Journal
Nat Rev Cancer 7:270-80 (2007)
DOI:10.1038/nrc2111
Reference
  Authors
Grassmann R, Aboud M, Jeang KT
  Title
Molecular mechanisms of cellular transformation by HTLV-1 Tax.
  Journal
Oncogene 24:5976-85 (2005)
DOI:10.1038/sj.onc.1208978
Reference
  Authors
Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L
  Title
The HTLV-1 Tax interactome.
  Journal
Retrovirology 5:76 (2008)
DOI:10.1186/1742-4690-5-76
Reference
  Authors
Jones KS, Lambert S, Bouttier M, Benit L, Ruscetti FW, Hermine O, Pique C
  Title
Molecular aspects of HTLV-1 entry: functional domains of the HTLV-1 surface subunit (SU) and their relationships to the entry receptors.
  Journal
Viruses 3:794-810 (2011)
DOI:10.3390/v3060794
Reference
  Authors
Ghez D, Lepelletier Y, Jones KS, Pique C, Hermine O
  Title
Current concepts regarding the HTLV-1 receptor complex.
  Journal
Retrovirology 7:99 (2010)
DOI:10.1186/1742-4690-7-99
Reference
  Authors
Sinet F.
  Title
Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: a number of proteins play a key role in the establishment and maintenance of viral infection.
  Journal
BioSciences Master Reviews, July 2013
Reference
  Authors
Sattentau Q
  Title
Avoiding the void: cell-to-cell spread of human viruses.
  Journal
Nat Rev Microbiol 6:815-26 (2008)
DOI:10.1038/nrmicro1972
Reference
  Authors
Vicente-Manzanares M, Sanchez-Madrid F
  Title
Role of the cytoskeleton during leukocyte responses.
  Journal
Nat Rev Immunol 4:110-22 (2004)
DOI:10.1038/nri1268
Reference
  Authors
Dutartre H, Claviere M, Journo C, Mahieux R
  Title
Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication.
  Journal
J Virol 90:7607-17 (2016)
DOI:10.1128/JVI.00407-16
Reference
  Authors
Awasthi S, Sharma A, Wong K, Zhang J, Matlock EF, Rogers L, Motloch P, Takemoto S, Taguchi H, Cole MD, Luscher B, Dittrich O, Tagami H, Nakatani Y, McGee M, Girard AM, Gaughan L, Robson CN, Monnat RJ Jr, Harrod R
  Title
A human T-cell lymphotropic virus type 1 enhancer of Myc transforming potential stabilizes Myc-TIP60 transcriptional interactions.
  Journal
Mol Cell Biol 25:6178-98 (2005)
DOI:10.1128/MCB.25.14.6178-6198.2005
Reference
  Authors
Edwards D, Fenizia C, Gold H, de Castro-Amarante MF, Buchmann C, Pise-Masison CA, Franchini G
  Title
Orf-I and orf-II-encoded proteins in HTLV-1 infection and persistence.
  Journal
Viruses 3:861-85 (2011)
DOI:10.3390/v3060861
Reference
  Authors
Nakano K, Watanabe T
  Title
HTLV-1 Rex Tunes the Cellular Environment Favorable for Viral Replication.
  Journal
Viruses 8:58 (2016)
DOI:10.3390/v8030058
Reference
  Authors
Shida H
  Title
Role of Nucleocytoplasmic RNA Transport during the Life Cycle of Retroviruses.
  Journal
Front Microbiol 3:179 (2012)
DOI:10.3389/fmicb.2012.00179
Reference
  Authors
Bai XT, Nicot C
  Title
Overview on HTLV-1 p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis.
  Journal
Front Microbiol 3:400 (2012)
DOI:10.3389/fmicb.2012.00400
Reference
  Authors
Taylor JM, Nicot C
  Title
HTLV-1 and apoptosis: role in cellular transformation and recent advances in therapeutic approaches.
  Journal
Apoptosis 13:733-47 (2008)
DOI:10.1007/s10495-008-0208-7
Reference
  Authors
D'Agostino DM, Silic-Benussi M, Hiraragi H, Lairmore MD, Ciminale V
  Title
The human T-cell leukemia virus type 1 p13II protein: effects on mitochondrial function and cell growth.
  Journal
Cell Death Differ 12 Suppl 1:905-15 (2005)
DOI:10.1038/sj.cdd.4401576
Reference
  Authors
Silic-Benussi M, Biasiotto R, Andresen V, Franchini G, D'Agostino DM, Ciminale V
  Title
HTLV-1 p13, a small protein with a busy agenda.
  Journal
Mol Aspects Med 31:350-8 (2010)
DOI:10.1016/j.mam.2010.03.001
Reference
  Authors
Fuentes-Gonzalez AM, Contreras-Paredes A, Manzo-Merino J, Lizano M
  Title
The modulation of apoptosis by oncogenic viruses.
  Journal
Virol J 10:182 (2013)
DOI:10.1186/1743-422X-10-182
Reference
  Authors
Qu Z, Xiao G
  Title
Human T-cell lymphotropic virus: a model of NF-kappaB-associated tumorigenesis.
  Journal
Viruses 3:714-49 (2011)
DOI:10.3390/v3060714
Reference
  Authors
Saggioro D
  Title
Anti-apoptotic effect of Tax: an NF-kappaB path or a CREB way?
  Journal
Viruses 3:1001-14 (2011)
DOI:10.3390/v3071001
Reference
  Authors
Harhaj EW, Harhaj NS
  Title
Mechanisms of persistent NF-kappaB activation by HTLV-I tax.
  Journal
IUBMB Life 57:83-91 (2005)
DOI:10.1080/15216540500078715
Reference
  Authors
Sun SC, Yamaoka S
  Title
Activation of NF-kappaB by HTLV-I and implications for cell transformation.
  Journal
Oncogene 24:5952-64 (2005)
DOI:10.1038/sj.onc.1208969
Reference
PMID:9710600
  Authors
Geleziunas R, Ferrell S, Lin X, Mu Y, Cunningham ET Jr, Grant M, Connelly MA, Hambor JE, Marcu KB, Greene WC
  Title
Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases.
  Journal
Mol Cell Biol 18:5157-65 (1998)
Reference
  Authors
Nakachi S, Nakazato T, Ishikawa C, Kimura R, Mann DA, Senba M, Masuzaki H, Mori N
  Title
Human T-cell leukemia virus type 1 tax transactivates the matrix metalloproteinase 7 gene via JunD/AP-1 signaling.
  Journal
Biochim Biophys Acta 1813:731-41 (2011)
DOI:10.1016/j.bbamcr.2011.02.002
Reference
  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
  Authors
Cherian MA, Baydoun HH, Al-Saleem J, Shkriabai N, Kvaratskhelia M, Green P, Ratner L
  Title
Akt Pathway Activation by Human T-cell Leukemia Virus Type 1 Tax Oncoprotein.
  Journal
J Biol Chem 290:26270-81 (2015)
DOI:10.1074/jbc.M115.684746
Reference
  Authors
Mori N, Morishita M, Tsukazaki T, Giam CZ, Kumatori A, Tanaka Y, Yamamoto N
  Title
Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor beta signaling through interaction with CREB-binding protein/p300.
  Journal
Blood 97:2137-44 (2001)
Reference
  Authors
Azran I, Schavinsky-Khrapunsky Y, Aboud M
  Title
Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity.
  Journal
Retrovirology 1:20 (2004)
DOI:10.1186/1742-4690-1-20
Reference
  Authors
Yoshida M
  Title
Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.
  Journal
Annu Rev Immunol 19:475-96 (2001)
DOI:10.1146/annurev.immunol.19.1.475
Reference
  Authors
Gabet AS, Mortreux F, Charneau P, Riou P, Duc-Dodon M, Wu Y, Jeang KT, Wattel E
  Title
Inactivation of hTERT transcription by Tax.
  Journal
Oncogene 22:3734-41 (2003)
DOI:10.1038/sj.onc.1206468
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