The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein.
Humans
Gene Products, tax
/ metabolism
Human T-lymphotropic virus 1
/ pathogenicity
Vascular Endothelial Growth Factor Receptor-2
/ metabolism
NF-kappa B
/ metabolism
Paraparesis, Tropical Spastic
/ virology
Cell Survival
Apoptosis
HTLV-I Infections
/ virology
CD4-Positive T-Lymphocytes
/ virology
T-Lymphocytes
/ metabolism
Leukemia-Lymphoma, Adult T-Cell
/ virology
Phosphorylation
HEK293 Cells
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 Jun 2024
25 Jun 2024
Historique:
received:
13
12
2023
accepted:
18
06
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
25
6
2024
Statut:
epublish
Résumé
Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and persistently activates NF-κB to maintain the viability of HTLV-1-infected T cells. Here, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR as an essential survival factor of HTLV-1-transformed cells. Inhibition of KDR specifically induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4 + T cells from HAM/TSP patients. Furthermore, inhibition of KDR triggers the autophagic degradation of Tax resulting in impaired NF-κB activation and diminished viral transmission in co-culture assays. Tax induces the expression of KDR, forms a complex with KDR, and is phosphorylated by KDR. These findings suggest that Tax stability is dependent on KDR activity which could be exploited as a strategy to target Tax in HTLV-1-associated diseases.
Identifiants
pubmed: 38918393
doi: 10.1038/s41467-024-49737-5
pii: 10.1038/s41467-024-49737-5
doi:
Substances chimiques
Gene Products, tax
0
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
NF-kappa B
0
tax protein, Human T-lymphotrophic virus 1
0
KDR protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5380Subventions
Organisme : NIAID NIH HHS
ID : R21 AI166335
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
Gessain, A. & Cassar, O. Epidemiological aspects and world distribution of HTLV-1 infection. Front. Microbiol. 3, 388 (2012).
pubmed: 23162541
pmcid: 3498738
doi: 10.3389/fmicb.2012.00388
Einsiedel, L. J., Pham, H., Woodman, R. J., Pepperill, C. & Taylor, K. A. The prevalence and clinical associations of HTLV-1 infection in a remote Indigenous community. Med. J. Aust. 205, 305–309 (2016).
pubmed: 27681971
doi: 10.5694/mja16.00285
Phillips, A. A. & Harewood, J. C. K. Adult T cell leukemia-lymphoma (ATL): state of the art. Curr. Hematol. Malignancy Rep. 13, 300–307 (2018).
doi: 10.1007/s11899-018-0458-6
Bangham, C. R., Araujo, A., Yamano, Y. & Taylor, G. P. HTLV-1-associated myelopathy/tropical spastic paraparesis. Nat. Rev. Dis. Prim. 1, 15012 (2015).
pubmed: 27188208
doi: 10.1038/nrdp.2015.12
Shimoyama, M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br. J. Haematol. 79, 428–437 (1991).
pubmed: 1751370
doi: 10.1111/j.1365-2141.1991.tb08051.x
El Hajj, H. et al. Novel treatments of adult T cell leukemia lymphoma. Front. Microbiol. 11, 1062 (2020).
pubmed: 32547515
pmcid: 7270167
doi: 10.3389/fmicb.2020.01062
Mohanty, S. & Harhaj, E. W. Mechanisms of oncogenesis by HTLV-1 Tax. Pathogens 9, 543 (2020).
Hleihel, R., Skayneh, H., de Thé, H., Hermine, O. & Bazarbachi, A. Primary cells from patients with adult T cell leukemia/lymphoma depend on HTLV-1 Tax expression for NF-kappaB activation and survival. Blood Cancer J. 13, 67 (2023).
pubmed: 37137914
pmcid: 10156663
doi: 10.1038/s41408-023-00841-7
Giebler, H. A. et al. Anchoring of CREB binding protein to the human T-cell leukemia virus type 1 promoter: a molecular mechanism of Tax transactivation. Mol. Cell Biol. 17, 5156–5164 (1997).
pubmed: 9271393
pmcid: 232366
doi: 10.1128/MCB.17.9.5156
Maeda, M. et al. IL-2/IL-2 receptor pathway plays a crucial role in the growth and malignant transformation of HTLV-1-infected T cells to develop adult T-cell leukemia. Front. Microbiol. 11, 356 (2020).
pubmed: 32210945
pmcid: 7067701
doi: 10.3389/fmicb.2020.00356
Migone, T. S. et al. Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I. Science 269, 79–81 (1995).
pubmed: 7604283
doi: 10.1126/science.7604283
Lavorgna, A., Matsuoka, M. & Harhaj, E. W. A critical role for IL-17RB signaling in HTLV-1 tax-induced NF-kappaB activation and T-cell transformation. PLoS Pathog. 10, e1004418 (2014).
pubmed: 25340344
pmcid: 4207800
doi: 10.1371/journal.ppat.1004418
Lavorgna, A. & Harhaj, E. W. Regulation of HTLV-1 tax stability, cellular trafficking and NF-kappaB activation by the ubiquitin-proteasome pathway. Viruses 6, 3925–3943 (2014).
pubmed: 25341660
pmcid: 4213571
doi: 10.3390/v6103925
Chiari, E. et al. Stable ubiquitination of human T-cell leukemia virus type 1 tax is required for proteasome binding. J. Virol. 78, 11823–11832 (2004).
pubmed: 15479824
pmcid: 523289
doi: 10.1128/JVI.78.21.11823-11832.2004
Shembade, N., Harhaj, N. S., Yamamoto, M., Akira, S. & Harhaj, E. W. The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation. J. Virol. 81, 13735–13742 (2007).
pubmed: 17942533
pmcid: 2168884
doi: 10.1128/JVI.01790-07
Gao, L. & Harhaj, E. W. HSP90 protects the human T-cell leukemia virus type 1 (HTLV-1) tax oncoprotein from proteasomal degradation to support NF-kappaB activation and HTLV-1 replication. J. Virol. 87, 13640–13654 (2013).
pubmed: 24109220
pmcid: 3838267
doi: 10.1128/JVI.02006-13
Ren, T. et al. HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains. Oncogene 34, 334–345 (2015).
pubmed: 24362528
doi: 10.1038/onc.2013.552
Tang, S. W., Chen, C. Y., Klase, Z., Zane, L. & Jeang, K. T. The cellular autophagy pathway modulates human T-cell leukemia virus type 1 replication. J. Virol. 87, 1699–1707 (2013).
pubmed: 23175371
pmcid: 3554132
doi: 10.1128/JVI.02147-12
Karkkainen, M. J. & Petrova, T. V. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene 19, 5598–5605 (2000).
pubmed: 11114740
doi: 10.1038/sj.onc.1203855
Singh, A. J. et al. A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis. Proc. Natl. Acad. Sci. USA 104, 5413–5418 (2007).
pubmed: 17372230
pmcid: 1828708
doi: 10.1073/pnas.0700809104
Zhou, H. J. et al. SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis. Nat. Commun. 9, 3303 (2018).
pubmed: 30120232
pmcid: 6098000
doi: 10.1038/s41467-018-05812-2
Ewan, L. C. et al. Intrinsic tyrosine kinase activity is required for vascular endothelial growth factor receptor 2 ubiquitination, sorting and degradation in endothelial cells. Traffic 7, 1270–1282 (2006).
pubmed: 17004325
doi: 10.1111/j.1600-0854.2006.00462.x
Ziegler, B. L. et al. KDR receptor: a key marker defining hematopoietic stem cells. Science 285, 1553–1558 (1999).
pubmed: 10477517
doi: 10.1126/science.285.5433.1553
Fiedler, W. et al. Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood 89, 1870–1875 (1997).
pubmed: 9058706
doi: 10.1182/blood.V89.6.1870
Shah, U. A. et al. North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies. Blood 132, 1507–1518 (2018).
pubmed: 30104217
pmcid: 6410908
doi: 10.1182/blood-2018-01-824607
Duke, E. S. et al. FDA approval summary: cabozantinib for differentiated thyroid cancer. Clin. Cancer Res. 28, 4173–4177 (2022).
pubmed: 35679021
pmcid: 9529996
doi: 10.1158/1078-0432.CCR-22-0873
Wang, X., Bove, A. M., Simone, G. & Ma, B. Molecular bases of VEGFR-2-mediated physiological function and pathological role. Front Cell Dev. Biol. 8, 599281 (2020).
pubmed: 33304904
pmcid: 7701214
doi: 10.3389/fcell.2020.599281
Katsuya, H. et al. The nature of the HTLV-1 provirus in naturally infected individuals analyzed by the viral DNA-capture-Seq approach. Cell Rep. 29, 724–735.e724 (2019).
pubmed: 31618639
doi: 10.1016/j.celrep.2019.09.016
Furuta, R. et al. Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo. PLoS Pathog. 13, e1006722 (2017).
pubmed: 29186194
pmcid: 5724899
doi: 10.1371/journal.ppat.1006722
Takeda, S. et al. Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells. Int. J. Cancer 109, 559–567 (2004).
pubmed: 14991578
doi: 10.1002/ijc.20007
Mohanty, S., Kumar, A., Das, P., Sahu, S. K. & Choudhuri, T. Multi-targeted therapy of everolimus in Kaposi’s sarcoma associated herpes virus infected primary effusion lymphoma. Apoptosis 22, 1098–1115 (2017).
pubmed: 28653223
doi: 10.1007/s10495-017-1391-1
Yu, F. F., Lin, X. L., Wang, X., Ping, Z. G. & Guo, X. Comparison of apoptosis and autophagy in human chondrocytes induced by the T-2 and HT-2 toxins. Toxins 11, 260 (2019).
Alefantis, T., Barmak, K., Harhaj, E. W., Grant, C. & Wigdahl, B. Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax. J. Biol. Chem. 278, 21814–21822 (2003).
pubmed: 12670929
doi: 10.1074/jbc.M211576200
Manickam, V. et al. Regulation of vascular endothelial growth factor receptor 2 trafficking and angiogenesis by Golgi localized t-SNARE syntaxin 6. Blood 117, 1425–1435 (2011).
pubmed: 21063020
pmcid: 3056478
doi: 10.1182/blood-2010-06-291690
Currer, R. et al. HTLV tax: a fascinating multifunctional co-regulator of viral and cellular pathways. Front. Microbiol. 3, 406 (2012).
pubmed: 23226145
pmcid: 3510432
doi: 10.3389/fmicb.2012.00406
Harhaj, N. S., Sun, S. C. & Harhaj, E. W. Activation of NF-kappaB by the human T cell leukemia virus type I Tax oncoprotein is associated with ubiquitin-dependent relocalization of IkappaB kinase. J. Biol. Chem. 282, 4185–4192 (2007).
pubmed: 17145747
doi: 10.1074/jbc.M611031200
Harhaj, E. W. & Giam, C. Z. NF-kappaB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma. FEBS J. 285, 3324–3336 (2018).
pubmed: 29722927
pmcid: 6750271
doi: 10.1111/febs.14492
Harhaj, E. W. et al. Somatic mutagenesis studies of NF-kappa B signaling in human T cells: evidence for an essential role of IKK gamma in NF-kappa B activation by T-cell costimulatory signals and HTLV-I Tax protein. Oncogene 19, 1448–1456 (2000).
pubmed: 10723136
doi: 10.1038/sj.onc.1203445
Nagai, M. et al. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J. Neurovirol. 4, 586–593 (1998).
pubmed: 10065900
doi: 10.3109/13550289809114225
Enose-Akahata, Y., Vellucci, A. & Jacobson, S. Role of HTLV-1 Tax and HBZ in the Pathogenesis of HAM/TSP. Front. Microbiol. 8, 2563 (2017).
pubmed: 29312243
pmcid: 5742587
doi: 10.3389/fmicb.2017.02563
Franchini, G., Wong-Staal, F. & Gallo, R. C. Human T-cell leukemia virus (HTLV-I) transcripts in fresh and cultured cells of patients with adult T-cell leukemia. Proc. Natl. Acad. Sci. USA 81, 6207–6211 (1984).
pubmed: 6091140
pmcid: 391889
doi: 10.1073/pnas.81.19.6207
Masaki, A. et al. Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) Tax-specific T-cell exhaustion in HTLV-1-infected individuals. Cancer Sci. 109, 2383–2390 (2018).
pubmed: 29845702
pmcid: 6113433
doi: 10.1111/cas.13654
Gessain, A., Louie, A., Gout, O., Gallo, R. C. & Franchini, G. Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy. J. Virol. 65, 1628–1633 (1991).
pubmed: 1995955
pmcid: 239951
doi: 10.1128/jvi.65.3.1628-1633.1991
Mahgoub, M. et al. Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells. Proc. Natl. Acad. Sci. USA 115, E1269–E1278 (2018).
Kulkarni, A. et al. Glucose metabolism and oxygen availability govern reactivation of the latent human retrovirus HTLV-1. Cell Chem. Biol. 24, 1377–1387.e1373 (2017).
pubmed: 28965728
pmcid: 5696563
doi: 10.1016/j.chembiol.2017.08.016
Vescovo, T., Pagni, B., Piacentini, M., Fimia, G. M. & Antonioli, M. Regulation of autophagy in cells infected with oncogenic human viruses and its impact on cancer development. Front Cell Dev. Biol. 8, 47 (2020).
pubmed: 32181249
pmcid: 7059124
doi: 10.3389/fcell.2020.00047
Lodewick, J., Lamsoul, I. & Bex, F. Move or die: the fate of the Tax oncoprotein of HTLV-1. Viruses 3, 829–857 (2011).
pubmed: 21994756
pmcid: 3185767
doi: 10.3390/v3060829
Lavorgna, A. & Harhaj, E. W. An RNA interference screen identifies the Deubiquitinase STAMBPL1 as a critical regulator of human T-cell leukemia virus type 1 tax nuclear export and NF-kappaB activation. J. Virol. 86, 3357–3369 (2012).
pubmed: 22258247
pmcid: 3302326
doi: 10.1128/JVI.06456-11
Lodewick, J. et al. Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-kappaB pathway. Virology 386, 68–78 (2009).
pubmed: 19200568
doi: 10.1016/j.virol.2008.12.043
Huang, J., Ren, T., Guan, H., Jiang, Y. & Cheng, H. HTLV-1 Tax is a critical lipid raft modulator that hijacks IkappaB kinases to the microdomains for persistent activation of NF-kappaB. J. Biol. Chem. 284, 6208–6217 (2009).
pubmed: 19129196
doi: 10.1074/jbc.M806390200
De Tito, S., Hervas, J. H., van Vliet, A. R. & Tooze, S. A. The Golgi as an assembly line to the autophagosome. Trends Biochem Sci. 45, 484–496 (2020).
pubmed: 32307224
doi: 10.1016/j.tibs.2020.03.010
Mori, N. et al. Interleukin-10 gene expression in adult T-cell leukemia. Blood 88, 1035–1045 (1996).
pubmed: 8704212
doi: 10.1182/blood.V88.3.1035.bloodjournal8831035
El Hajj, H. et al. Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells. Haematologica 106, 1443–1456 (2021).
pubmed: 33567810
pmcid: 8094094
doi: 10.3324/haematol.2020.264523
El-Sabban, M. E. et al. Human T-cell lymphotropic virus type 1-transformed cells induce angiogenesis and establish functional gap junctions with endothelial cells. Blood 99, 3383–3389 (2002).
pubmed: 11964307
doi: 10.1182/blood.V99.9.3383
Kchour, G. et al. Zidovudine and interferon-alpha treatment induces a high response rate and reduces HTLV-1 proviral load and VEGF plasma levels in patients with adult T-cell leukemia from North East Iran. Leuk. Lymphoma 48, 330–336 (2007).
pubmed: 17325893
doi: 10.1080/10428190601071717
Kchour, G. et al. Increased microvessel density in involved organs from patients with HTLV-I associated adult T cell leukemia lymphoma. Leuk. Lymphoma 49, 265–270 (2008).
pubmed: 18231912
doi: 10.1080/10428190701760060
Watters, K. M., Dean, J., Gautier, V., Hall, W. W. & Sheehy, N. Tax 1-independent induction of vascular endothelial growth factor in adult T-cell leukemia caused by human T-cell leukemia virus type 1. J. Virol. 84, 5222–5228 (2010).
pubmed: 20237090
pmcid: 2863836
doi: 10.1128/JVI.02166-09
Watters, K. M. et al. Cytokine and growth factor expression by HTLV-1 Lck-tax transgenic cells in SCID mice. AIDS Res. Hum. Retroviruses 26, 593–603 (2010).
pubmed: 20438380
doi: 10.1089/aid.2009.0212
Saito, M. et al. Serum concentration and genetic polymorphism in the 5’-untraslated region of VEGF is not associated with susceptibility to HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-I infected individuals. J. Neurol. Sci. 219, 157–161 (2004).
pubmed: 15050452
doi: 10.1016/j.jns.2004.01.009
Freitas, N. L. et al. Lessons from the cerebrospinal fluid analysis of HTLV-1-infected individuals: biomarkers of inflammation for HAM/TSP development. Viruses 14, 2146 (2022).
Zong, Y. et al. Safety of intraocular anti-VEGF antibody treatment under in vitro HTLV-1 infection. Front. Immunol. 13, 1089286 (2022).
pubmed: 36761168
doi: 10.3389/fimmu.2022.1089286
Lambert, S. et al. HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165. Blood 113, 5176–5185 (2009).
pubmed: 19270265
pmcid: 2686187
doi: 10.1182/blood-2008-04-150342
Durkin, S. S., Ward, M. D., Fryrear, K. A. & Semmes, O. J. Site-specific phosphorylation differentiates active from inactive forms of the human T-cell leukemia virus type 1 Tax oncoprotein. J. Biol. Chem. 281, 31705–31712 (2006).
pubmed: 16923801
doi: 10.1074/jbc.M607011200
Krause Boehm, A. et al. Analysis of potential phosphorylation sites in human T cell leukemia virus type 1 Tax. J. Biomed. Sci. 6, 206–212 (1999).
pubmed: 10343169
doi: 10.1159/000025388
Bex, F., Murphy, K., Wattiez, R., Burny, A. & Gaynor, R. B. Phosphorylation of the human T-cell leukemia virus type 1 transactivator tax on adjacent serine residues is critical for tax activation. J. Virol. 73, 738–745 (1999).
pubmed: 9847380
pmcid: 103881
doi: 10.1128/JVI.73.1.738-745.1999
Futsch, N., Mahieux, R. & Dutartre, H. HTLV-1, the other pathogenic yet neglected human retrovirus: from transmission to therapeutic treatment. Viruses 10, 1 (2017).
Gill, P. S. et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. New Engl. J. Med. 332, 1744–1748 (1995).
pubmed: 7760890
doi: 10.1056/NEJM199506293322603
Cook, L. B. et al. Long-term clinical remission maintained after cessation of zidovudine and interferon-alpha therapy in chronic adult T-cell leukemia/lymphoma. Int. J. Hematol. 107, 378–382 (2018).
pubmed: 29090417
doi: 10.1007/s12185-017-2361-7
Dassouki, Z. et al. ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation. Blood 125, 474–482 (2015).
pubmed: 25395419
doi: 10.1182/blood-2014-04-572750
Kondo, N. et al. Involvement of EZH2 inhibition in lenalidomide and pomalidomide-mediated growth suppression in HTLV-1-infected cells. Biochem Biophys. Res. Commun. 574, 104–109 (2021).
pubmed: 34455369
doi: 10.1016/j.bbrc.2021.08.051
Ishida, T. et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J. Clin. Oncol. 30, 837–842 (2012).
pubmed: 22312108
doi: 10.1200/JCO.2011.37.3472
Kawata, T. et al. Tucidinostat restores CCR4 expression in adult T-cell leukemia/lymphoma. Haematologica 109, 1007 (2023).
Koseki, A. et al. EZH1/2 dual inhibitors suppress HTLV-1-infected cell proliferation and hyperimmune response in HTLV-1-associated myelopathy. Front. Microbiol. 14, 1175762 (2023).
pubmed: 37378292
pmcid: 10291084
doi: 10.3389/fmicb.2023.1175762
Kannagi, M. et al. Maintenance of long remission in adult T-cell leukemia by Tax-targeted vaccine: A hope for disease-preventive therapy. Cancer Sci. 110, 849–857 (2019).
pubmed: 30666755
pmcid: 6398881
doi: 10.1111/cas.13948
Araujo, A. et al. Management of HAM/TSP: Systematic Review and Consensus-based Recommendations 2019. Neurol. Clin. Pr. 11, 49–56 (2021).
doi: 10.1212/CPJ.0000000000000832
Olindo, S. et al. Safety of long-term treatment of HAM/TSP patients with valproic acid. Blood 118, 6306–6309 (2011).
pubmed: 21998206
doi: 10.1182/blood-2011-04-349910
Uhlik, M. et al. NF-kappaB-inducing kinase and IkappaB kinase participate in human T-cell leukemia virus I Tax-mediated NF-kappaB activation. J. Biol. Chem. 273, 21132–21136 (1998).
pubmed: 9694868
doi: 10.1074/jbc.273.33.21132
Miura, H., Maeda, M., Yamamoto, N. & Yamaoka, S. Distinct IkappaB kinase regulation in adult T cell leukemia and HTLV-I-transformed cells. Exp. Cell Res. 308, 29–40 (2005).
pubmed: 15878527
doi: 10.1016/j.yexcr.2005.04.005
Kwon, H. et al. Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus Tax. J. Biol. Chem. 280, 35713–35722 (2005).
pubmed: 16105841
doi: 10.1074/jbc.M504848200
Harhaj, E. W. & Sun, S. C. IKKgamma serves as a docking subunit of the IkappaB kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein. J. Biol. Chem. 274, 22911–22914 (1999).
pubmed: 10438454
doi: 10.1074/jbc.274.33.22911
Mohanty, S. et al. RETRA induces necroptosis in cervical cancer cells through RIPK1, RIPK3, MLKL and increased ROS production. Eur. J. Pharm. 920, 174840 (2022).
doi: 10.1016/j.ejphar.2022.174840
Mohanty, S. et al. The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-kappaB activation. PLoS Pathog. 16, e1008504 (2020).
pubmed: 33362245
pmcid: 7790423
doi: 10.1371/journal.ppat.1008504
Stokes, M. P. et al. Complementary PTM profiling of drug response in human gastric carcinoma by immunoaffinity and IMAC methods with total proteome analysis. Proteomes 3, 160–183 (2015).
pubmed: 28248267
pmcid: 5217380
doi: 10.3390/proteomes3030160
Eng, J. K., Jahan, T. A. & Hoopmann, M. R. Comet: an open-source MS/MS sequence database search tool. Proteomics 13, 22–24 (2013).
pubmed: 23148064
doi: 10.1002/pmic.201200439