School of Life Sciences, Tsinghua University, Beijing 100084, China.
Biochem Biophys Res Commun. 2011 Apr 1;407(1):254-9. doi: 10.1016/j.bbrc.2011.03.016. Epub 2011 Mar 5.
Krüppel-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.
Krüppel 样因子 2（KLF2）对于正常的肺发育、红系分化、T 细胞分化、迁移和归巢至关重要。然而，KLF2 的调节机制，特别是其负责的 E3 连接酶，仍不清楚。在这里，我们发现同源物 E6AP 羧基末端（HECT）型泛素连接酶 Smad 泛素化调节因子 1（Smurf1）与 KLF2 相互作用，并特异性地将 KLF2 靶向多泛素化和蛋白酶体降解，特别是在肺癌 H1299 细胞中。Smurf1 的催化连接酶活性对于调节 KLF2 是必需的。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。本研究首次证明 Smurf1 作为 E3 连接酶，促进 KLF2 的泛素化和蛋白酶体降解。
