Volume 8 Supplement 1
HTLV-1 Tax1 represses the proapoptotic protein Bim, which is crucial for T-cell transformation
© Higuchi and Fujii; licensee BioMed Central Ltd. 2011
Published: 6 June 2011
Human T cell leukemia virus type 1 (HTLV-1) is an etiological agent of adult T-cell leukemia (ATL) and its viral oncoprotein Tax1 plays critical roles in T cell transformation and ATL development. Tax1 converts a T-cell line CTLL-2 from IL-2 dependent growth into IL-2-independent one, and the conversion requires inhibition of apoptosis. In this study, we investigated the involvement of Bim, an apoptosis inducer after cytokine deprivation, in Tax1-induced transformation. Bim expression is strongly induced in CTLL-2 cells after IL-2 starvation, whereas such induction is markedly reduced in CTLL-2 cells transformed by Tax1. A Tax1 mutant defective of NF-kB2 activation transformed CTLL-2 less efficiently than wild type Tax, but this low transforming activity was rescued by knockdown of Bim in CTLL-2, suggesting that activation of noncanonical NF-kB2 pathway is involved in Tax1-mediated Bim repression. Furthermore, the expression of Bim was lower in HTLV-1 transformed and ATL cell lines than HTLV-1-negative T-cell lines. These results suggest that the Bim repression by Tax1 is crucial for the survival of HTLV-1 infected cells and may play a role in ATL development.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.