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Journal of Virology, June 2009, p. 5339-5352, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00232-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dimerization and a Novel Tax Speckled Structure Localization Signal Are Required for Tax Nuclear Localization{triangledown}

Kimberly A. Fryrear, Sarah S. Durkin, Saurabh K. Gupta, Jessica B. Tiedebohl, and O. John Semmes*

Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 W. Olney Road, Norfolk, Virginia 23507

Received 2 February 2009/ Accepted 2 March 2009

The human T-cell leukemia virus type 1 oncoprotein Tax has pleiotropic activities, a subset of which likely leads to immortalization of T cells. Tax is expressed and known to function in both the cell nucleus and the cytoplasm. Tax has defined nuclear localization (NLS) and nuclear export signals that enable shuttling between the two compartments. In this study, we identified a novel region in Tax that targets the protein to discrete nuclear foci that we have previously termed Tax speckled structures (TSS). We demonstrated that the identified region is both necessary and sufficient for directing proteins to TSS. This novel TSS localization signal (TSLS), spanning amino acids 50 to 75, is separable from and adjacent to the NLS of Tax. Coexpression of a Tax NLS mutant and a Tax TSLS mutant rescued the nuclear entry and subnuclear TSS targeting of both proteins, demonstrating that these signals are independent domains. Our analysis also revealed that Tax proteins deficient for dimerization fail to localize to the nucleus. Consequently, when we restored dimerization via induction of a heterologous "dimerizer" domain, nuclear localization was rescued. Thus, we defined additional domains in Tax specific for nuclear localization and subnuclear targeting. Our results reveal a more complex network for regulation of Tax subcellular localization and subsequent function.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Cell Biology, Lewis Hall, 700 West Olney Road, Norfolk, VA 23507. Phone: (757) 446-5904. Fax: (757) 446-5766. E-mail: semmesoj{at}evms.edu

{triangledown} Published ahead of print on 25 March 2009.

Journal of Virology, June 2009, p. 5339-5352, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00232-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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