Thioredoxin-binding protein-2 (TBP-2/VDUP1/TXNIP) regulates T-cell sensitivity to glucocorticoid during HTLV-I-induced transformation.
Thioredoxin-binding protein-2 (TBP-2/VDUP1/TXNIP) regulates T-cell sensitivity to glucocorticoid during HTLV-I-induced transformation.
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DOI：
10.1038/leu.2010.286
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发表时间：
2011-03
期刊：
影响因子：
11.4
通讯作者：
Yodoi, J.
中科院分区：
文献类型：
--
作者：
Chen, Z.;Lopez-Ramos, D. A.;Yoshihara, E.;Maeda, Y.;Masutani, H.;Sugie, K.;Maeda, M.;Yodoi, J.
关键词：
虽然糖皮质激素（GC）被广泛用于治疗包括成人T细胞白血病（ATL）在内的造血系统恶性肿瘤，但白血病细胞在临床过程中对GC产生耐药性的机制仍不清楚。用人类嗜T淋巴细胞病毒Ⅰ型（HTLV-Ⅰ）感染T细胞系，观察了T细胞由白细胞介素2（IL-2）依赖性生长期向非依赖性生长期的转化。这种转化与硫氧还蛋白结合蛋白2（TBP-2）的丢失有关，TBP-2是一种肿瘤抑制因子和脂质代谢调节因子。在这里，我们表明，TBP-2是负责GC诱导的ATL细胞凋亡。在IL-2依赖阶段，地塞米松诱导TBP-2表达和凋亡，这两个都被GC受体（GR）拮抗剂RU 486阻断。TBP-2的敲低一致地减少GC诱导的细胞凋亡的量。IL-2非依赖期GR和TBP-2表达受抑制，GC不能诱导细胞凋亡。GR的强制表达导致细胞对GC的轻度敏感性，这也是通过用TBP-2诱导剂辛二酰苯胺异羟肟酸处理来实现的。转染实验表明，TBP-2表达诱导IL-2非依赖性ATL细胞凋亡。因此，TBP-2可能是GC诱导细胞凋亡的关键分子之一，也是治疗晚期ATL的潜在靶点。
Although glucocorticoid (GC) is widely used for treating hematopoietic malignancies including adult T-cell leukemia (ATL), the mechanism by which leukemic cells become resistant to GC in the clinical course remains unclear. Using a series of T-cell lines infected with human T lymphotropic virus type-I (HTLV-I), the causative virus of ATL, we have dissected the transformation from interleukin (IL)-2-dependent to -independent growth stage. The transformation associates the loss of thioredoxin-binding protein-2 (TBP-2), a tumor suppressor and regulator of lipid metabolism. Here we show that TBP-2 is responsible for GC-induced apoptosis in ATL cells. In the IL-2-dependent stage, dexamethasone induced TBP-2 expression and apoptosis, both of which were blocked by GC receptor (GR) antagonist RU486. Knockdown of TBP-2 consistently reduced the amount of GC-induced apoptosis. In IL-2-independent stage, however, expression of GR and TBP-2 was suppressed and GC failed to induce apoptosis. Forced expression of GR led the cells to mild sensitivity to GC, which was also accomplished by treatment with suberoylanilide hydroxamic acid, a TBP-2 inducer. A transfection experiment showed that TBP-2 expression induced apoptosis in IL-2-independent ATL cells. Thus, TBP-2 is likely to be one of the key molecules for GC-induced apoptosis and a potential target for treating the advanced stage of ATL.
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影响因子：
2.6
作者：
Mukherjee, A.;Martin, S. G.
通讯作者：
Martin, S. G.
DOI：
10.1073/pnas.77.12.7415
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
POIESZ, BJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
5.4
作者：
Higuchi, Masaya;Tsubata, Chikako;Fujii, Masahiro
通讯作者：
Fujii, Masahiro
影响因子：
8
作者：
Ahsan, MK;Masutani, H;Yodoi, J
通讯作者：
Yodoi, J
影响因子：
11.2
作者：
Nishinaka, Y;Nishiyama, A;Yodoi, J
通讯作者：
Yodoi, J