文献类型：期刊文献

英文题名：Activation of the cyclin D2 and cdk6 genes through NF-κB is critical for cell-cycle progression induced by HTLV-I Tax

作者：Iwanaga, R.[2];Ozono, E.[3];Fujisawa, J.[4];Ikeda, M. A.[3];Okamura, N.[2];Huang, Y.[5];Ohtani, K.[1]

机构：[1]Tokyo Med & Dent Univ, Human Gene Sci Ctr, Bunkyo Ku, Tokyo 1138510, Japan;[2]Tokyo Med & Dent Univ, Grad Sch Hlth Sci, Lab Microbiol & Immunol, Tokyo 1138510, Japan;[3]Tokyo Med & Dent Univ, Grad Sch, Sect Mol Embryol, Tokyo, Japan;[4]Kansai Med Univ, Dept Microbiol, Osaka, Japan;[5]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut Sci, Shanghai 200237, Peoples R China

年份：2008

卷号：27

期号：42

起止页码：5635

外文期刊名：ONCOGENE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000259280800009)】；

语种：英文

外文关键词：HTLV-I; Tax; cell cycle; E2F; cyclin D2; cdk6

摘要：Human T-cell leukemia virus type I (HTLV-I) can infect a variety of cell types, so the cause of T-cell-specific oncogenesis remains to be elucidated. The trans-activator protein Tax of HTLV-I can promote cell-cycle progression in resting T cells along with induction of cyclin D2 and cyclin-dependent kinase (cdk6) gene expression. Here, we found that Tax cannot induce cell-cycle progression in resting fibroblasts and analysed the molecular basis of the cell-type specificity. Tax activated cyclin D2 and cdk6 promoters in T cells, but not in fibroblasts, depending on its ability to activate the transcription factor nuclear factor (NF)-kappa B. Expression of cyclin D2 and CDK6 activated the transcription factor E2F, which is essential for cell-cycle progression, in both T cells and fibroblasts. Short-hairpin RNA (shRNA)-mediated inhibition of cyclin D2 and CDK6 induction suppressed Tax-induced activation of E2F in T cells. Finally, shRNA-mediated downregulation of NF-kappa B p65 or p100 expression reduced Tax-induced activation of cyclin D2 and/or cdk6 promoters and cell-cycle progression in T cells. These results indicate that Tax-induced cell-cycle progression in T cells is mediated, at least in part, through cell-type-specific activation of the cyclin D2 and cdk6 genes through NF-kappa B and may be important for the cell-type-specific oncogenesis.