The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process
The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process
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DOI：
10.1196/annals.1323.002
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Yodoi, J
中科院分区：
文献类型：
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作者：
Yoshida, T;Nakamura, H;Yodoi, J
最近关于衰老的报告显示，许多影响寿命的基因位点与产生或防御氧化应激的机制密切相关。因此，对抗氧化应激的保护机制在对抗衰老过程中很重要。硫氧还蛋白（TRX）是一种小巯基介导的蛋白质，在保守的活性位点内具有氧化还原活性的二硫键/二巯基。TRX转基因小鼠比对照小鼠更能抵抗各种氧化应激，包括感染和炎症。此外，我们观察到TRX tg小鼠的中位寿命与对照组相比延长了135%。TRX结合蛋白-2（TBP-2）与维生素D3上调蛋白1（VDUP 1）相同，被鉴定为TRX的结合分子和TRX功能的负调节因子。TBP-2 VDUP 1的表达在肿瘤组织和细胞系中经常丢失，并且TBP-2NDUP 1的异位表达沿着细胞周期停滞在G1期而抑制细胞增殖。这些发现表明，TRX和TBP-2NDUP 1不仅参与细胞保护功能，对抗氧化应激，而且还参与细胞增殖和衰老过程的调节。
Recent reports on aging have revealed that many genetic loci affecting life span are closely linked to the machinery either producing or defending oxidative stress. Protective mechanisms against oxidative stress are thus important in countering the aging process. Thioredoxin (TRX) is a small thiol-mediated protein with a redox-active disulfide/dithiol within the conserved active site. TRX transgenic mice are more resistant than control mice to a variety of oxidative stresses including infection and inflammation. Moreover, we observed that the median life span of TRX tg mice was extended up to 135% compared to that of controls. TRX binding protein-2 (TBP-2), which is identical to vitamin D3 upregulated protein 1 (VDUP1), was identified as a binding molecule to TRX, and a negative regulator of TRX function. The expression of TBP-2VDUP1 is frequently lost in tumor tissue and cell lines, and ectopic expression of TBP-2NDUP1 suppresses cellular proliferation along with cell cycle arrest at the G, phase. These findings suggest that TRX and TBP-2NDUP1 are involved not only in cytoprotective functions against oxidative stress, but also in the regulation of cellular proliferation and the aging process.