Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-Cell transformation: Implications for adult T-Cell leukemia leukemogenesis
Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-Cell transformation: Implications for adult T-Cell leukemia leukemogenesis
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DOI：
10.1158/0008-5472.can-03-0908
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发表时间：
2004-02-15
期刊：
影响因子：
11.2
通讯作者：
Yodoi, J
中科院分区：
文献类型：
--
作者：
Nishinaka, Y;Nishiyama, A;Yodoi, J
人t细胞白血病病毒I型（HTLV-I）是成人t细胞白血病（ATL）的病原体。然而，在htlv -i感染的携带者中，ATL的发病率较低，潜伏期较长，这表明多个宿主-病毒事件参与了htlv -i依赖性转化的进展和ATL的后续发展。人硫氧还蛋白（TRX）是htlv - i转化细胞系中高度表达的氧化还原活性蛋白，而TRX结合蛋白-2/维生素D3上调蛋白1 （TBP-2/VDUP1）最近被发现是TRX的负调控蛋白。我们在这里报道，TBP-2的表达在htlv - 1阳性、白细胞介素-2独立的t细胞系中缺失，但在htlv - 1阳性、白细胞介素-2依赖的t细胞系以及htlv - 1阴性的t细胞系中保持。htlv - i阳性T细胞中TBP-2异位过表达导致生长抑制。在过表达tbp -2的细胞中，观察到G(1)阻滞与p16表达增加和视网膜母细胞瘤磷酸化降低有关。结果表明，TBP-2在T细胞的生长调控中起着至关重要的作用，htlv -i感染的T细胞中TBP-2表达的缺失是ATL白血病发生多步骤进展的关键事件之一。
Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia (ATL). However, the low incidence of ATL among HTLV-I-infected carriers, together with a long latent period, suggests that multiple host-viral events are involved in the progression of HTLV-I-dependent transformation and subsequent development of ATL. Human thioredoxin (TRX) is a redox active protein highly expressed in HTLV-I-transformed cell lines, whereas the TRX-binding protein-2/vitamin D3 up-regulated protein 1 (TBP-2/VDUP1) was recently identified as a negative regulator of TRX. We report here that expression of TBP-2 is lost in HTLV-I-positive, interleukin-2-independent T-cell lines but maintained in HTLV-I-positive, interleukin-2-dependent T-cell lines, as well as HTLV-I-negative T-cell lines. Ectopic overexpression of TBP-2 in HTLV-I-positive T cells resulted in growth suppression. In the TBP-2-overexpressing cells, a G(1) arrest was observed in association with an increase of p16 expression and reduction of retinoblastoma phosphorylation. The results suggest that TBP-2 plays a crucial role in the growth regulation of T cells and that the loss of TBP-2 expression in HTLV-I-infected T cells is one of the key events involved in the multistep progression of ATL leukemogenesis.