This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nicot, C.
Right arrow Articles by Giam, C.-Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nicot, C.
Right arrow Articles by Giam, C.-Z.

 Previous Article  |  Next Article 

J Virol, August 1998, p. 6777-6784, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cytoplasmic Forms of Human T-Cell Leukemia Virus Type 1 Tax Induce NF-kappa B Activation

Christophe Nicot, Feng Tie,dagger and Chou-Zen Giam*

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814

Received 18 August 1997/Accepted 4 May 1998

Human T-cell leukemia virus type 1 (HTLV-1) Tax targets I-kappa Balpha and I-kappa Bbeta for phosphorylation, ubiquitination, and proteasome-mediated degradation, causing the nuclear translocation of NF-kappa B/Rel proteins and transcription induction of many cellular genes. The mechanism by which a nuclear protein such as Tax stimulates I-kappa B phosphorylation and degradation remains unclear. Here, we describe two cytoplasmic mutants of Tax, designated TaxDelta N81 and TaxDelta N109, from which the domains important for cyclic AMP response element binding factor (CREB) and serum response factor (SRF) binding and nuclear transport have been removed. These mutants were unable to trans activate from the HTLV-1 21-bp repeats or the serum response element in the c-fos promoter. In contrast, they activated NF-kappa B reporters, suggesting that activation of NF-kappa B by Tax occurs in the cytoplasm. Incorporation of the nuclear localization signal (NLS) of the simian virus 40 large T antigen into TaxDelta N81 and TaxDelta N109 redirected both proteins predominantly to the nucleus yet did not restore trans activation via CREB or SRF. The NLS fusion had little effect on TaxDelta N81 but reduced NF-kappa B trans activation by TaxDelta N109, possibly because of its proximity to the NF-kappa B-activating domain of Tax. In contrast to wild-type Tax, the cytoplasmic TaxDelta N mutants are not cytotoxic. Stable expression of TaxDelta N109 in HeLa cells resulted in a significant reduction in the intracellular level of I-kappa Balpha , with the constitutive presence of NF-kappa B in the nucleus and concomitant activation of the NF-kappa B enhancer. These results are suggestive of a potential application of the TaxDelta N109-like mutants in targeting I-kappa B degradation and NF-kappa B activation. Interestingly, a Tax species with a molecular mass similar to that of TaxDelta N109 was identified in many HTLV-1-transformed T cells, suggesting that TaxDelta N109-like species might play a role in HTLV-1-induced leukemogenesis.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799. Phone: (301) 295-9624. Fax: (301) 295-1545. E-mail: giam{at}bob.usuf2.usuhs.mil.

dagger Present address: Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106.

J Virol, August 1998, p. 6777-6784, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Nejmeddine, M., Negi, V. S., Mukherjee, S., Tanaka, Y., Orth, K., Taylor, G. P., Bangham, C. R. M. (2009). HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse. Blood 114: 1016-1025 [Abstract] [Full Text]  
  • Fryrear, K. A., Durkin, S. S., Gupta, S. K., Tiedebohl, J. B., Semmes, O. J. (2009). Dimerization and a Novel Tax Speckled Structure Localization Signal Are Required for Tax Nuclear Localization. J. Virol. 83: 5339-5352 [Abstract] [Full Text]  
  • Tsuji, T., Sheehy, N., Gautier, V. W., Hayakawa, H., Sawa, H., Hall, W. W. (2007). The Nuclear Import of the Human T Lymphotropic Virus Type I (HTLV-1) Tax Protein Is Carrier- and Energy-independent. J. Biol. Chem. 282: 13875-13883 [Abstract] [Full Text]  
  • Younis, I., Yamamoto, B., Phipps, A., Green, P. L. (2005). Human T-Cell Leukemia Virus Type 1 Expressing Nonoverlapping Tax and Rex Genes Replicates and Immortalizes Primary Human T Lymphocytes but Fails To Replicate and Persist In Vivo. J. Virol. 79: 14473-14481 [Abstract] [Full Text]  
  • Alefantis, T., Mostoller, K., Jain, P., Harhaj, E., Grant, C., Wigdahl, B. (2005). Secretion of the Human T Cell Leukemia Virus Type I Transactivator Protein Tax. J. Biol. Chem. 280: 17353-17362 [Abstract] [Full Text]  
  • Meertens, L., Chevalier, S., Weil, R., Gessain, A., Mahieux, R. (2004). 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. 279: 43307-43320 [Abstract] [Full Text]  
  • Wu, K., Bottazzi, M. E., de la Fuente, C., Deng, L., Gitlin, S. D., Maddukuri, A., Dadgar, S., Li, H., Vertes, A., Pumfery, A., Kashanchi, F. (2004). Protein Profile of Tax-associated Complexes. J. Biol. Chem. 279: 495-508 [Abstract] [Full Text]  
  • Alefantis, T., Barmak, K., Harhaj, E. W., Grant, C., Wigdahl, B. (2003). Characterization of a Nuclear Export Signal within the Human T Cell Leukemia Virus Type I Transactivator Protein Tax. J. Biol. Chem. 278: 21814-21822 [Abstract] [Full Text]  
  • Liang, M.-H., Geisbert, T., Yao, Y., Hinrichs, S. H., Giam, C.-Z. (2002). Human T-Lymphotropic Virus Type 1 Oncoprotein Tax Promotes S-Phase Entry but Blocks Mitosis. J. Virol. 76: 4022-4033 [Abstract] [Full Text]  
  • Liao, C.-L., Lin, Y.-L., Wu, B.-C., Tsao, C.-H., Wang, M.-C., Liu, C.-I, Huang, Y.-L., Chen, J.-H., Wang, J.-P., Chen, L.-K. (2001). Salicylates Inhibit Flavivirus Replication Independently of Blocking Nuclear Factor Kappa B Activation. J. Virol. 75: 7828-7839 [Abstract] [Full Text]  
  • Nicot, C., Harrod, R. (2000). Distinct p300-Responsive Mechanisms Promote Caspase-Dependent Apoptosis by Human T-Cell Lymphotropic Virus Type 1 Tax Protein. Mol. Cell. Biol. 20: 8580-8589 [Abstract] [Full Text]  
  • Harrod, R., Kuo, Y.-L., Tang, Y., Yao, Y., Vassilev, A., Nakatani, Y., Giam, C.-Z. (2000). p300 and p300/cAMP-responsive Element-binding Protein Associated Factor Interact with Human T-cell Lymphotropic Virus Type-1 Tax in a Multi-histone Acetyltransferase/Activator-Enhancer Complex. J. Biol. Chem. 275: 11852-11857 [Abstract] [Full Text]  
  • Burton, M., Upadhyaya, C. D., Maier, B., Hope, T. J., Semmes, O. J. (2000). Human T-Cell Leukemia Virus Type 1 Tax Shuttles between Functionally Discrete Subcellular Targets. J. Virol. 74: 2351-2364 [Abstract] [Full Text]  
  • Kimzey, A. L., Dynan, W. S. (1999). Identification of a Human T-cell Leukemia Virus Type I Tax Peptide in Contact with DNA. J. Biol. Chem. 274: 34226-34232 [Abstract] [Full Text]  
  • Li, X. H., Murphy, K. M., Palka, K. T., Surabhi, R. M., Gaynor, R. B. (1999). The Human T-cell Leukemia Virus Type-1 Tax Protein Regulates the Activity of the Ikappa B Kinase Complex. J. Biol. Chem. 274: 34417-34424 [Abstract] [Full Text]  
  • Marusawa, H., Hijikata, M., Chiba, T., Shimotohno, K. (1999). Hepatitis C Virus Core Protein Inhibits Fas- and Tumor Necrosis Factor Alpha-Mediated Apoptosis via NF-kappa B Activation. J. Virol. 73: 4713-4720 [Abstract] [Full Text]  
  • Harrod, R., Tang, Y., Nicot, C., Lu, H. S., Vassilev, A., Nakatani, Y., Giam, C.-Z. (1998). An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300. Mol. Cell. Biol. 18: 5052-5061 [Abstract] [Full Text]  
  • Xiao, G., Harhaj, E. W., Sun, S.-C. (2000). Domain-specific Interaction with the Ikappa B Kinase (IKK) Regulatory Subunit IKKgamma Is an Essential Step in Tax-mediated Activation of IKK. J. Biol. Chem. 275: 34060-34067 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»