Jeon Jun-Ho, Lee Kee-Nyung, Hwang Chae Young, Kwon Ki-Sun, You Kwan-Hee, Choi Inpyo
Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, Republic of Korea.
Cancer Res. 2005 Jun 1;65(11):4485-9. doi: 10.1158/0008-5472.CAN-04-2271.
Vitamin D3 up-regulated protein 1 (VDUP1) is a stress-response gene that is up-regulated by 1,25(OH)2D3 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 VDUP1-/- 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(kip1) stability. In this process, VDUP1 blocked the JAB1-mediated translocation of p27(kip1) 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.
维生素D3上调蛋白1（VDUP1）是一种应激反应基因，在许多细胞中受1,25(OH)2D3上调。据报道，许多肿瘤细胞中VDUP1表达降低，而VDUP1的强制表达通过阻止细胞周期进程来抑制细胞增殖。在此，我们发现与野生型细胞相比，VDUP1基因敲除的成纤维细胞增殖更快，且细胞周期蛋白依赖性激酶抑制剂p27（kip1）的表达降低。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诱导的对p27（kip1）稳定性的抑制作用。在此过程中，VDUP1阻止了JAB1介导的p27（kip1）从细胞核向细胞质的转运。此外，VDUP1抑制JAB1介导的激活蛋白-1的激活及细胞增殖。综上所述，这些结果表明VDUP1是通过调节JAB1来影响p-27（kip1）稳定性的新因子。
