{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:28:09Z","timestamp":1791080889149,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Retrovirology"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Human T-cell leukemia virus type 1 and type 2 are related human retroviruses. HTLV-1 is the etiological agent of the Adult T-cell Leukemia\/Lymphoma and of the Tropical Spastic Paraparesis\/HTLV-1 Associated Myelopathy, whereas, HTLV-2 infection has not been formally associated with any T-cell malignancy. HTLV-1 and 2 genomes encode, respectively, the Tax1 and Tax2 proteins whose role is to transactivate the viral promoter. HTLV-1 and HTLV-2 Tax sequences display 28% divergence at the amino acid level. Tax1 is a shuttling protein that possesses both a non canonical nuclear import (NLS) and a nuclear export (NES) signal. We have recently demonstrated that Tax1 and Tax2 display different subcellular localization and that residues 90\u2013100 are critical for this process. We investigate in the present report, whether Tax2 also possesses a functional NES.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We first used a NES prediction method to determine whether the Tax2 protein might contain a NES and the results do suggest the presence of a NES sequence in Tax2. Using Green Fluorescent Protein-NES (GFP-NES) fusion proteins, we demonstrate that the Tax2 sequence encompasses a functional NES (NES2). As shown by microscope imaging, NES2 is able to mediate translocation of GFP from the nucleus, without the context of a full length Tax protein. Furthermore, point mutations or leptomycin B treatment abrogate NES2 function. However, within the context of full length Tax2, similar point mutations in the NES2 leucine rich stretch do not modify Tax2 localization. Finally, we also show that Tax1 NES function is dependent upon the positioning of the nuclear export signal \"vis-\u00e0-vis\" GFP.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>HTLV-2 Tax NES is functional but dispensable for the protein localization <jats:italic>in vitro<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1742-4690-2-70","type":"journal-article","created":{"date-parts":[[2005,11,15]],"date-time":"2005-11-15T07:14:58Z","timestamp":1132038898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Presence of a functional but dispensable Nuclear Export Signal in the HTLV-2 Tax protein"],"prefix":"10.1186","volume":"2","author":[{"given":"S\u00e9bastien A","family":"Chevalier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Meertens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Calattini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Gessain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Kiemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Mahieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,11,14]]},"reference":[{"issue":"39","key":"116_CR1","doi-asserted-by":"publisher","first-page":"5996","DOI":"10.1038\/sj.onc.1208971","volume":"24","author":"G Feuer","year":"2005","unstructured":"Feuer G, Green PL: Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2. Oncogene. 2005, 24 (39): 5996-6004. 10.1038\/sj.onc.1208971.","journal-title":"Oncogene"},{"issue":"8452","key":"116_CR2","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/S0140-6736(85)92734-5","volume":"2","author":"A Gessain","year":"1985","unstructured":"Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de The G: Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985, 2 (8452): 407-410. 10.1016\/S0140-6736(85)92734-5.","journal-title":"Lancet"},{"issue":"2","key":"116_CR3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1212\/WNL.48.2.315","volume":"48","author":"EL Murphy","year":"1997","unstructured":"Murphy EL, Fridey J, Smith JW, Engstrom J, Sacher RA, Miller K, Gibble J, Stevens J, Thomson R, Hansma D, Kaplan J, Khabbaz R, Nemo G: HTLV-associated myelopathy in a cohort of HTLV-I and HTLV-II-infected blood donors. The REDS investigators. Neurology. 1997, 48 (2): 315-320.","journal-title":"Neurology"},{"issue":"12","key":"116_CR4","doi-asserted-by":"publisher","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","volume":"77","author":"BJ Poiesz","year":"1980","unstructured":"Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC: Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980, 77 (12): 7415-7419.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"39","key":"116_CR5","doi-asserted-by":"publisher","first-page":"5976","DOI":"10.1038\/sj.onc.1208978","volume":"24","author":"R Grassmann","year":"2005","unstructured":"Grassmann R, Aboud M, Jeang KT: Molecular mechanisms of cellular transformation by HTLV-1 Tax. Oncogene. 2005, 24 (39): 5976-5985. 10.1038\/sj.onc.1208978.","journal-title":"Oncogene"},{"issue":"31","key":"116_CR6","doi-asserted-by":"publisher","first-page":"31991","DOI":"10.1074\/jbc.R400009200","volume":"279","author":"KT Jeang","year":"2004","unstructured":"Jeang KT, Giam CZ, Majone F, Aboud M: Life, death, and tax: role of HTLV-I oncoprotein in genetic instability and cellular transformation. J Biol Chem. 2004, 279 (31): 31991-31994. 10.1074\/jbc.R400009200.","journal-title":"J Biol Chem"},{"issue":"15","key":"116_CR7","doi-asserted-by":"publisher","first-page":"6866","DOI":"10.1128\/JVI.74.15.6866-6874.2000","volume":"74","author":"R Mahieux","year":"2000","unstructured":"Mahieux R, Pise-Masison CA, Lambert PF, Nicot C, De Marchis L, Gessain A, Green P, Hall W, Brady JN: Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 tax to inhibit p53 function. J Virol. 2000, 74 (15): 6866-6874. 10.1128\/JVI.74.15.6866-6874.2000.","journal-title":"J Virol"},{"issue":"16","key":"116_CR8","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1089\/08892220050193137","volume":"16","author":"R Mahieux","year":"2000","unstructured":"Mahieux R, Pise-Masison CA, Nicot C, Green P, Hall WW, Brady JN: Inactivation of p53 by HTLV type 1 and HTLV type 2 Tax trans-activators. AIDS Res Hum Retroviruses. 2000, 16 (16): 1677-1681. 10.1089\/08892220050193137.","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"11","key":"116_CR9","doi-asserted-by":"crossref","first-page":"8912","DOI":"10.1128\/jvi.71.11.8912-8917.1997","volume":"71","author":"TM Ross","year":"1997","unstructured":"Ross TM, Minella AC, Fang ZY, Pettiford SM, Green PL: Mutational analysis of human T-cell leukemia virus type 2 Tax. J Virol. 1997, 71 (11): 8912-8917.","journal-title":"J Virol"},{"issue":"8","key":"116_CR10","doi-asserted-by":"crossref","first-page":"5194","DOI":"10.1128\/jvi.70.8.5194-5202.1996","volume":"70","author":"TM Ross","year":"1996","unstructured":"Ross TM, Pettiford SM, Green PL: The tax gene of human T-cell leukemia virus type 2 is essential for transformation of human T lymphocytes. J Virol. 1996, 70 (8): 5194-5202.","journal-title":"J Virol"},{"issue":"1","key":"116_CR11","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1006\/viro.1996.0126","volume":"217","author":"OJ Semmes","year":"1996","unstructured":"Semmes OJ, Majone F, Cantemir C, Turchetto L, Hjelle B, Jeang KT: HTLV-I and HTLV-II Tax: differences in induction of micronuclei in cells and transcriptional activation of viral LTRs. Virology. 1996, 217 (1): 373-379. 10.1006\/viro.1996.0126.","journal-title":"Virology"},{"issue":"19","key":"116_CR12","doi-asserted-by":"publisher","first-page":"10399","DOI":"10.1128\/JVI.78.19.10399-10409.2004","volume":"78","author":"M Sieburg","year":"2004","unstructured":"Sieburg M, Tripp A, Ma JW, Feuer G: Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 tax oncoproteins modulate cell cycle progression and apoptosis. J Virol. 2004, 78 (19): 10399-10409. 10.1128\/JVI.78.19.10399-10409.2004.","journal-title":"J Virol"},{"issue":"12","key":"116_CR13","doi-asserted-by":"crossref","first-page":"8508","DOI":"10.1128\/jvi.70.12.8508-8517.1996","volume":"70","author":"Y Tanaka","year":"1996","unstructured":"Tanaka Y, Hayashi M, Takagi S, Yoshie O: Differential transactivation of the intercellular adhesion molecule 1 gene promoter by Tax1 and Tax2 of human T-cell leukemia viruses. J Virol. 1996, 70 (12): 8508-8517.","journal-title":"J Virol"},{"issue":"22","key":"116_CR14","doi-asserted-by":"publisher","first-page":"12152","DOI":"10.1128\/JVI.77.22.12152-12164.2003","volume":"77","author":"A Tripp","year":"2003","unstructured":"Tripp A, Liu Y, Sieburg M, Montalbano J, Wrzesinski S, Feuer G: Human T-cell leukemia virus type 1 tax oncoprotein suppression of multilineage hematopoiesis of CD34+ cells in vitro. J Virol. 2003, 77 (22): 12152-12164. 10.1128\/JVI.77.22.12152-12164.2003.","journal-title":"J Virol"},{"key":"116_CR15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1742-4690-2-46","volume":"2","author":"C Tsubata","year":"2005","unstructured":"Tsubata C, Higuchi M, Takahashi M, Oie M, Tanaka Y, Gejyo F, Fujii M: PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line. Retrovirology. 2005, 2: 46-10.1186\/1742-4690-2-46.","journal-title":"Retrovirology"},{"issue":"41","key":"116_CR16","doi-asserted-by":"publisher","first-page":"43307","DOI":"10.1074\/jbc.M400497200","volume":"279","author":"L Meertens","year":"2004","unstructured":"Meertens L, Chevalier S, Weil R, Gessain A, Mahieux R: A 10-amino acid domain within human T-cell leukemia virus type 1 and type 2 tax protein sequences is responsible for their divergent subcellular distribution. J Biol Chem. 2004, 279 (41): 43307-43320. 10.1074\/jbc.M400497200.","journal-title":"J Biol Chem"},{"issue":"32","key":"116_CR17","doi-asserted-by":"publisher","first-page":"5447","DOI":"10.1038\/sj.onc.1207719","volume":"23","author":"L Meertens","year":"2004","unstructured":"Meertens L, Pise-Masison C, Quere N, Brady J, Gessain A, Mahieux R: Utilization of the CBP but not the p300 co-activator by human T-lymphotropic virus type-2 Tax for p53 inhibition. Oncogene. 2004, 23 (32): 5447-5458. 10.1038\/sj.onc.1207719.","journal-title":"Oncogene"},{"issue":"18","key":"116_CR18","doi-asserted-by":"publisher","first-page":"11925","DOI":"10.1128\/JVI.79.18.11925-11934.2005","volume":"79","author":"A Niinuma","year":"2005","unstructured":"Niinuma A, Higuchi M, Takahashi M, Oie M, Tanaka Y, Gejyo F, Tanaka N, Sugamura K, Xie L, Green PL, Fujii M: Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus. J Virol. 2005, 79 (18): 11925-11934. 10.1128\/JVI.79.18.11925-11934.2005.","journal-title":"J Virol"},{"issue":"6","key":"116_CR19","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1128\/JVI.76.6.2648-2653.2002","volume":"76","author":"K Endo","year":"2002","unstructured":"Endo K, Hirata A, Iwai K, Sakurai M, Fukushi M, Oie M, Higuchi M, Hall WW, Gejyo F, Fujii M: Human T-cell leukemia virus type 2 (HTLV-2) Tax protein transforms a rat fibroblast cell line but less efficiently than HTLV-1 Tax. J Virol. 2002, 76 (6): 2648-2653. 10.1128\/JVI.76.6.2648-2653.2002.","journal-title":"J Virol"},{"issue":"4","key":"116_CR20","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.tibs.2004.02.006","volume":"29","author":"B Fahrenkrog","year":"2004","unstructured":"Fahrenkrog B, Koser J, Aebi U: The nuclear pore complex: a jack of all trades?. Trends Biochem Sci. 2004, 29 (4): 175-182. 10.1016\/j.tibs.2004.02.006.","journal-title":"Trends Biochem Sci"},{"issue":"3","key":"116_CR21","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nrm1331","volume":"5","author":"L Xu","year":"2004","unstructured":"Xu L, Massague J: Nucleocytoplasmic shuttling of signal transducers. Nat Rev Mol Cell Biol. 2004, 5 (3): 209-219. 10.1038\/nrm1331.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"23","key":"116_CR22","doi-asserted-by":"publisher","first-page":"10246","DOI":"10.1128\/MCB.24.23.10246-10255.2004","volume":"24","author":"C Quensel","year":"2004","unstructured":"Quensel C, Friedrich B, Sommer T, Hartmann E, Kohler M: In vivo analysis of importin alpha proteins reveals cellular proliferation inhibition and substrate specificity. Mol Cell Biol. 2004, 24 (23): 10246-10255. 10.1128\/MCB.24.23.10246-10255.2004.","journal-title":"Mol Cell Biol"},{"issue":"6","key":"116_CR23","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1093\/protein\/gzh062","volume":"17","author":"T la Cour","year":"2004","unstructured":"la Cour T, Kiemer L, Molgaard A, Gupta R, Skriver K, Brunak S: Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel. 2004, 17 (6): 527-536. 10.1093\/protein\/gzh062.","journal-title":"Protein Eng Des Sel"},{"issue":"1","key":"116_CR24","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/nar\/gkg101","volume":"31","author":"T la Cour","year":"2003","unstructured":"la Cour T, Gupta R, Rapacki K, Skriver K, Poulsen FM, Brunak S: NESbase version 1.0: a database of nuclear export signals. Nucleic Acids Res. 2003, 31 (1): 393-396. 10.1093\/nar\/gkg101.","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"116_CR25","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1128\/MCB.25.2.728-739.2005","volume":"25","author":"D Daelemans","year":"2005","unstructured":"Daelemans D, Costes SV, Lockett S, Pavlakis GN: Kinetic and molecular analysis of nuclear export factor CRM1 association with its cargo in vivo. Mol Cell Biol. 2005, 25 (2): 728-739. 10.1128\/MCB.25.2.728-739.2005.","journal-title":"Mol Cell Biol"},{"issue":"9","key":"116_CR26","doi-asserted-by":"publisher","first-page":"741","DOI":"10.2174\/0929867033457791","volume":"10","author":"Y Yashiroda","year":"2003","unstructured":"Yashiroda Y, Yoshida M: Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs. Curr Med Chem. 2003, 10 (9): 741-748. 10.2174\/0929867033457791.","journal-title":"Curr Med Chem"},{"issue":"24","key":"116_CR27","doi-asserted-by":"publisher","first-page":"21814","DOI":"10.1074\/jbc.M211576200","volume":"278","author":"T Alefantis","year":"2003","unstructured":"Alefantis T, Barmak K, Harhaj EW, 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. 2003, 278 (24): 21814-21822. 10.1074\/jbc.M211576200.","journal-title":"J Biol Chem"},{"issue":"4714","key":"116_CR28","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1126\/science.2992082","volume":"229","author":"BK Felber","year":"1985","unstructured":"Felber BK, Paskalis H, Kleinman-Ewing C, Wong-Staal F, Pavlakis GN: The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985, 229 (4714): 675-679.","journal-title":"Science"},{"issue":"4691","key":"116_CR29","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1126\/science.2983419","volume":"227","author":"WC Goh","year":"1985","unstructured":"Goh WC, Sodroski J, Rosen C, Essex M, Haseltine WA: Subcellular localization of the product of the long open reading frame of human T-cell leukemia virus type I. Science. 1985, 227 (4691): 1227-1228.","journal-title":"Science"},{"issue":"2","key":"116_CR30","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/0042-6822(85)90149-7","volume":"147","author":"T Kiyokawa","year":"1985","unstructured":"Kiyokawa T, Kawaguchi T, Seiki M, Yoshida M: Association of the pX gene product of human T-cell leukemia virus type-I with nucleus. Virology. 1985, 147 (2): 462-465. 10.1016\/0042-6822(85)90149-7.","journal-title":"Virology"},{"issue":"4706","key":"116_CR31","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1126\/science.2990027","volume":"228","author":"DJ Slamon","year":"1985","unstructured":"Slamon DJ, Press MF, Souza LM, Murdock DC, Cline MJ, Golde DW, Gasson JC, Chen IS: Studies of the putative transforming protein of the type I human T-cell leukemia virus. Science. 1985, 228 (4706): 1427-1430.","journal-title":"Science"},{"issue":"1","key":"116_CR32","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/0042-6822(92)90320-O","volume":"187","author":"MR Smith","year":"1992","unstructured":"Smith MR, Greene WC: Characterization of a novel nuclear localization signal in the HTLV-I tax transactivator protein. Virology. 1992, 187 (1): 316-320. 10.1016\/0042-6822(92)90320-O.","journal-title":"Virology"},{"issue":"9","key":"116_CR33","doi-asserted-by":"crossref","first-page":"6347","DOI":"10.1128\/jvi.70.9.6347-6357.1996","volume":"70","author":"OJ Semmes","year":"1996","unstructured":"Semmes OJ, Jeang KT: Localization of human T-cell leukemia virus type 1 tax to subnuclear compartments that overlap with interchromatin speckles. J Virol. 1996, 70 (9): 6347-6357.","journal-title":"J Virol"},{"issue":"5","key":"116_CR34","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.1128\/JVI.74.5.2351-2364.2000","volume":"74","author":"M Burton","year":"2000","unstructured":"Burton M, Upadhyaya CD, Maier B, Hope TJ, Semmes OJ: Human T-cell leukemia virus type 1 Tax shuttles between functionally discrete subcellular targets. J Virol. 2000, 74 (5): 2351-2364. 10.1128\/JVI.74.5.2351-2364.2000.","journal-title":"J Virol"},{"key":"116_CR35","unstructured":"Turci M, Romanelli MG, Lorenzi P, Righi P, Bertazzoni U: Localization of HTLV-2 Tax protein is dependent upon a nuclear localization determinant in the N-terminal region. Gene"},{"issue":"6","key":"116_CR36","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/S0092-8674(00)80371-2","volume":"90","author":"M Fornerod","year":"1997","unstructured":"Fornerod M, Ohno M, Yoshida M, Mattaj IW: CRM1 is an export receptor for leucine-rich nuclear export signals. Cell. 1997, 90 (6): 1051-1060. 10.1016\/S0092-8674(00)80371-2.","journal-title":"Cell"},{"issue":"39","key":"116_CR37","doi-asserted-by":"publisher","first-page":"5952","DOI":"10.1038\/sj.onc.1208969","volume":"24","author":"SC Sun","year":"2005","unstructured":"Sun SC, Yamaoka S: Activation of NF-kappaB by HTLV-I and implications for cell transformation. Oncogene. 2005, 24 (39): 5952-5964. 10.1038\/sj.onc.1208969.","journal-title":"Oncogene"}],"container-title":["Retrovirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-4690-2-70.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T02:42:41Z","timestamp":1630464161000},"score":1,"resource":{"primary":{"URL":"https:\/\/retrovirology.biomedcentral.com\/articles\/10.1186\/1742-4690-2-70"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,14]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["116"],"URL":"https:\/\/doi.org\/10.1186\/1742-4690-2-70","relation":{},"ISSN":["1742-4690"],"issn-type":[{"value":"1742-4690","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,14]]},"assertion":[{"value":"14 October 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"70"}}