Molecular basis for the expression of major vault protein induced by hyperosmotic stress in SW620 human colon cancer cells.
Molecular basis for the expression of major vault protein induced by hyperosmotic stress in SW620 human colon cancer cells.
复制标题
DOI：
10.3892/ijmm.2013.1428
复制
发表时间：
2013-09
影响因子：
5.4
通讯作者：
Yusuke Tajitsu;R. Ikeda;Yukihiko Nishizawa;Hirofumi Mataki;Xiao-Fang Che;T. Sumizawa;Mina Nitta;Tatsuya Yamaguchi;Masatatsu Yamamoto;Sho Tabata;S. Akiyama;Katsushi Yamada;T. Furukawa;Yasuo Takeda
中科院分区：
文献类型：
--
作者：
Yusuke Tajitsu;R. Ikeda;Yukihiko Nishizawa;Hirofumi Mataki;Xiao-Fang Che;T. Sumizawa;Mina Nitta;Tatsuya Yamaguchi;Masatatsu Yamamoto;Sho Tabata;S. Akiyama;Katsushi Yamada;T. Furukawa;Yasuo Takeda
主要拱顶蛋白(MVP)与肺阻力相关蛋白(LRP)相同，肺阻力相关蛋白是拱顶的主要成分。拱顶被认为对外来物质和其他类型的压力起到了保护作用。在先前的研究中，我们曾报道在含有蔗糖的高渗培养液中，SW620人结肠癌细胞中MVP的表达水平增加。然而，渗透胁迫诱导MVP表达的分子机制尚未阐明。因此，在本研究中，我们探讨了渗透胁迫诱导MVP表达的机制。在高渗胁迫条件下，特异性蛋白1(Sp1)的泛素化程度降低，Sp1蛋白水平升高，与MVP启动子的结合增强，针对Sp1的小干扰RNA(SiRNA)抑制MVP表达的诱导。在高渗条件下，c-Jun氨基末端激酶(JNK)的特异性抑制剂SP600125可抑制MVP和Sp1的表达。我们的结果表明，JNK对Sp1蛋白表达的稳定和上调参与了抑制Sp1的泛素化和降解，从而诱导了高渗条件下MVP的表达。
Major vault protein (MVP) is identical to lung resistance-related protein (LRP), which is the major component of vaults. Vaults are considered to play a protective role against xenobiotics and other types of stress. In a previous study, we reported that the expression levels of MVP in SW620 human colon cancer cells were increased in hypertonic culture medium with sucrose. However, the molecular mechanism behind the induction of MVP expression by osmotic stress has not yet been elucidated. Therefore, in the present study, we investigated the mechanism behind the induction of MVP expression by osmotic stress. Under hyperosmotic stress conditions, the ubiquitination of specificity protein 1 (Sp1) decreased, Sp1 protein levels increased, its binding to the MVP promoter was enhanced, and small interfering RNA (siRNA) for Sp1 suppressed the induction of MVP expression. The inhibition of c-jun N-terminal kinase (JNK) by SP600125, a specific JNK inhibitor, decreased the expression of MVP and Sp1 under hyperosmotic conditions. Our data indicate that the stabilization and upregulation of Sp1 protein expression by JNK participate in the inhibition of the ubiquitination and degradation of Sp1, and thus in the induction of MVP expression under hyperosmotic conditions.