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Journal of Virology, November 2004, p. 11686-11695, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11686-11695.2004

Ubiquitination of Human T-Cell Leukemia Virus Type 1 Tax Modulates Its Activity

Jean-Marie Peloponese Jr.,^1, Hidekatsu Iha,^1, Venkat R. K. Yedavalli,¹ Akiko Miyazato,¹ Yan Li,¹ Kerstin Haller,¹ Monsef Benkirane,² and Kuan-Teh Jeang^1*

Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,¹ CNRS UPR1142, Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, Montpellier, France²

Received 15 April 2004/ Accepted 24 June 2004

Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein. Tax is a transcriptional activator which modulates expression of the viral long terminal repeat and transcription of many cellular genes. Because Tax is a critical HTLV-1 factor which mediates viral transformation of T cells during the genesis of adult T-cell leukemia, it is important to understand the processes which can activate or inactivate Tax function. Here, we report that ubiquitination of Tax is a posttranscriptional mechanism which regulates Tax function. We show that ubiquitination does not target Tax for degradation by the proteasome. Rather, ubiquitin addition modifies Tax in a proteasome-independent manner from an active to a less-active transcriptional form.

Contributed equally to this paper.

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