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

✍ Scribed by Naoki Mori; Masahiro Fujii; Michael Hinz; Katsushi Nakayama; Yasuaki Yamada; Shuichi Ikeda; Yoshihiro Yamasaki; Fatah Kashanchi; Yuetsu Tanaka; Masao Tomonaga; Naoki Yamamoto

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: French
• Weight: 444 KB
• Volume: 99
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.10388

✦ Synopsis

Abstract

Our aim was to examine the involvement of G~1~ 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‐κB failed to activate cyclin D1 and D2 promoters. Inhibitors of NF‐κB (dominant negative IκBs mutants) suppressed Tax‐dependent activation of cyclin D1 and D2 promoters, indicating that Tax‐induced activation was mediated by NF‐κB. Wild‐type and mutant Tax capable of activating NF‐κB, but not Tax mutant incapable of activating NF‐κB, 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. © 2002 Wiley‐Liss, Inc.