Tumor suppressor VDUP1 increases p27kip1 stability by inhibiting JAB1
Tumor suppressor VDUP1 increases p27kip1 stability by inhibiting JAB1
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DOI：
10.1158/0008-5472.can-04-2271
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发表时间：
2005-06-01
期刊：
影响因子：
11.2
通讯作者：
Choi, I
中科院分区：
文献类型：
--
作者：
Jeon, JH;Lee, KN;Choi, I
维生素D-3上调蛋白1（VDUP1）是一种应力反应基因，在许多细胞中被1,25（OH）（2）D-3上调。据报道，VDUP1在许多肿瘤细胞中的表达降低，VDUP1的强制表达通过阻止细胞周期进展来抑制细胞的增殖。在这里，我们发现VDUPI - / - 成纤维细胞与野生型细胞（一种依赖细胞周期蛋白依赖性激酶抑制剂的表达降低）相比，增殖的速度更快。已知JAB1与P27（KIP1）相互作用并降低P27（KIP1）的稳定性。 VDUP1与JAB1相互作用，并恢复了JAB1诱导的P27 KIPL稳定性的抑制。在此过程中，VDUP1阻止了P27 KIPP从细胞核到细胞质的JAB1介导的易位。此外，VDUP1抑制了JAB1介导的激活蛋白-1激活和细胞增殖。综上所述，这些结果表明VDUP1是通过调节JAB1的P27（KIP1）稳定性的新因素。
Vitamin D-3 up-regulated protein 1 (VDUP1) is a stress-response gene that is up-regulated by 1,25(OH)(2)D-3 in many cells. It has been reported that VDUP1 expression is reduced in many tumor cells and the enforced expression of VDUP1 inhibits cell proliferation by arresting cell cycle progression. Here, we found that VDUPI-/- fibroblast cells proliferated more rapidly compared with wild-type cells with reduced expression of p27(kip1), a cyclin-dependent kinase inhibitor. JAB1 is known to interact with p27(kip1) and to decrease the stability of p27(kip1). VDUP1 interacted with JAB1 and restored JAB1-induced suppression of p27 kipl stability. In this process, VDUP1 blocked the JAB1-mediated translocation of p27 kipl from the nucleus to the cytoplasm. In addition, VDUP1 inhibited JAB1-mediated activator protein-1 activation and cell proliferation. Taken together, these results indicate that VDUP1 is a novel factor of p27(kip1) stability via regulating JAB1.