Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I tax protein is associated with IL-2-independent growth of T cells

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Item Type:	Article
Title:	Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I tax protein is associated with IL-2-independent growth of T cells
Creators Name:	Mori, N., Fujii, M., Hinz, M., Nakayama, K., Yamada, Y., Ikeda, S., Yamasaki, Y., Kashanchi, F., Tanaka, Y., Tomonaga, M. and Yamamoto, N.
Abstract:	Our aim was to examine the involvement of G1 cell-cycle regulators in cell growth dysregulation induced by HTLV-I. Compared to uninfected cells, higher expression levels of cyclin D1 and D2 mRNA were detected in HTLV-I–infected T-cell lines, which were at least in part mediated by the viral transforming protein Tax since Tax activated both cyclin D1 and D2 promoters in the human T-cell line Jurkat. A Tax mutant that did not activate NF-{kappa}B failed to activate cyclin D1 and D2 promoters. Inhibitors of NF-{kappa}B (dominant negative I{kappa}Bs mutants) suppressed Tax-dependent activation of cyclin D1 and D2 promoters, indicating that Tax-induced activation was mediated by NF-{kappa}B. Wild-type and mutant Tax capable of activating NF-{kappa}B, but not Tax mutant incapable of activating NF-{kappa}B, converted cell growth of a T-cell line from being IL-2–dependent to being IL-2–independent; and this conversion was associated with IL-2–independent induction of cyclins D1 and D2. Our data suggest that induction of cyclins D1 and D2 by Tax is involved in IL-2–independent cell-cycle progression as well as IL-2–independent transformation of primary human T cells by HTLV-I. High expression levels of cyclin D1 and D2 mRNAs were also detected in some patients with ATL. Our findings link HTLV-I infection to changes in cellular D-type cyclin gene expression, transformation of T cells and subsequent development of T-cell leukemia.
Keywords:	Cyclin D1, Cyclin D2, Human T-Cell Leukemia Virus Type I, Tax, NF-{kappa}B, Animals, Mice
Source:	International Journal of Cancer
ISSN:	0020-7136
Publisher:	Wiley
Volume:	99
Number:	3
Page Range:	378-385
Date:	20 May 2002
Official Publication:	https://doi.org/10.1002/ijc.10388
PubMed:	View item in PubMed

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