Smurf1 ubiquitin ligase targets Kruppel-like factor KLF2 for ubiquitination and degradation in human lung cancer H1299 cells
Smurf1 ubiquitin ligase targets Kruppel-like factor KLF2 for ubiquitination and degradation in human lung cancer H1299 cells
复制标题
Smurf1 泛素连接酶靶向 Kruppel 样因子 KLF2 在人肺癌 H1299 细胞中泛素化和降解
DOI：
10.1016/j.bbrc.2011.03.016
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发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Zhang, Lingqiang
中科院分区：
文献类型：
--
作者：
Xie, Ping;Tang, Ying;Zhang, Lingqiang
Kruppel样因子2（KLF2）已被证明是肺正常发育，红细胞分化，T细胞分化，迁移和归巢所必需的。然而，KLF 2的调节机制，特别是其负责的E3连接酶，仍然不清楚。在这里，我们表明，同源E6AP羧基末端（HECT）型泛素连接酶Smad泛素化调节因子1（Smurf1）相互作用，并针对KLF2的多聚泛素化和蛋白酶体降解，特别是在肺癌H1299细胞。Smurf1的催化连接酶活性是其调节KLF2所必需的。因此，Smurf1抑制KLF2的转录因子活性，并调节其下游基因如CD62L和Wee1的表达。这项研究提供了第一个证据表明，Smurf1作为E3连接酶的功能，以促进泛素化和蛋白酶体降解KLF2。(C)2011 Elsevier Inc. All rights reserved.
Kruppel-like factor 2 (KLF2) has been demonstrated to be essential for normal lung development, erythroid differentiation, T-cell differentiation, migration and homing. However, the mechanisms underlying the regulation of KLF2, in particular its responsible E3 ligase is still unclear. Here we show that the homologous to E6AP carboxyl terminus (HECT)-type ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) interacts with and targets KLF2 for poly-ubiquitination and proteasomal degradation specifically in lung cancer H1299 cells. The catalytic ligase activity of Smurf1 is required for it to regulate KLF2. Consequently, Smurf1 represses the transcriptional factor activity of KLF2 and regulates the expression its downstream genes such as CD62L and Wee1. This study provided the first evidence that Smurf1 functions as an E3 ligase to promote the ubiquitination and proteasomal degradation of KLF2. (C) 2011 Elsevier Inc. All rights reserved.