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Journal of Virology, November 2001, p. 11106-11115, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11106-11115.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human T-Cell Leukemia Virus Type 1 Tax Protein Binds to Assembled Nuclear Proteasomes and Enhances Their Proteolytic Activity

Joris Hemelaar,1,* Françoise Bex,2 Bruce Booth,1 Vincenzo Cerundolo,1 Andrew McMichael,3 and Susan Daenke1,dagger

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU,1 and MRC Human Immunology Unit, Institute of Molecular Medicine, Oxford OX3 9DS,3 United Kingdom, and Laboratoire de Microbiologie, Université Libre de Bruxelles, B-1070 Brussels, Belgium2

Received 4 April 2001/Accepted 8 August 2001

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates the HTLV-1 long terminal repeat and key regulatory proteins involved in inflammation, activation, and proliferation and may induce cell transformation. Tax is also the immunodominant target antigen for cytotoxic T cells in HTLV-1 infection. We found that Tax bound to assembled nuclear proteasomes, but Tax could not be detected in the cytoplasm. Confocal microscopy revealed a partial colocalization of Tax with nuclear proteasomes. As Tax translocated into the nucleus very quickly after synthesis, this process probably takes place prior to and independent of proteasome association. Tax mutants revealed that both the Tax N and C termini play a role in proteasome binding. We also found that proteasomes from Tax-transfected cells had enhanced proteolytic activity on prototypic peptide substrates. This effect was not due to the induction of the LMP2 and LMP7 proteasome subunits. Furthermore, Tax appeared to be a long-lived protein, with a half-life of around 15 h. These data suggest that the association of Tax with the proteasome and the enhanced proteolytic activity do not target Tax for rapid degradation and may not determine its immunodominance.

* Corresponding author. Mailing address: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Level 7, Room 7508, Oxford OX3 9DU, United Kingdom. Phone: 44-(0)1865-221349. Fax: 44-(0)1865-220993. E-mail: hemelaar{at}pinnacle.jr2.ox.ac.uk.

dagger Present address: Empyrika Ltd., John Eccles House, The Oxford Science Park, Oxford OX4 4GP, United Kingdom.

Journal of Virology, November 2001, p. 11106-11115, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11106-11115.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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