Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein
Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein
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DOI：
10.1186/1742-4690-3-71
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发表时间：
2006-10-17
期刊：
影响因子：
3.3
通讯作者：
Fujii, Masahiro
中科院分区：
文献类型：
--
作者：
Ishioka, Kojiro;Higuchi, Masaya;Fujii, Masahiro
背景：人类T细胞白血病病毒1型(HTLV-1)Tax1蛋白与肿瘤抑制基因Dlg1的相互作用与细胞转化相关。结果：我们发现，通过RNA干扰敲除Dlg1可以增加Tax1转化小鼠T细胞系(CTLL-2)的能力，这是通过测量白介素2(IL)-2的非依赖性生长来衡量的。与野生型Tax1相比，缺乏Dlg1相互作用的Tax1突变体对CTLL-2的转化减少，但Dlg1还原对转化的影响最小。转化的少数Tax1 Delta C转导的CTLL2细胞的Dlg1表达低于亲代细胞，提示Tax1 Delta C选择性地转化了Dlg1-low细胞。此外，HTLV-1永生化的人T细胞系，包括含有Tax1 Delta C的重组HTLV-1，其Dlg1的表达均低于对照T细胞。结论：Dlg1的失活增强了Tax1介导的CTLL2的转化，除Dlg1外，PDZ蛋白(S)在转化过程中起关键作用。
Background: The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1 protein with the tumor suppressor Dlg1 is correlated with cellular transformation.Results: Here, we show that Dlg1 knockdown by RNA interference increases the ability of Tax1 to transform a mouse T-cell line (CTLL-2), as measured interleukin (IL)-2-independent growth. A Tax1 mutant defective for the Dlg1 interaction showed reduced transformation of CTLL-2 compared to wild type Tax1, but the transformation was minimally affected by Dlg1 reduction. The few Tax1 Delta C-transduced CTLL-2 cells that became transformed expressed less Dlg1 than parental cells, suggesting that Dlg1-low cells were selectively transformed by Tax1 Delta C. Moreover, all human T-cell lines immortalized by HTLV-1, including the recombinant HTLV-1-containing Tax1 Delta C, expressed less Dlg1 than control T-cell lines.Conclusion: These results suggest that inactivation of Dlg1 augments Tax1-mediated transformation of CTLL-2, and PDZ protein(s) other than Dlg1 are critically involved in the transformation.