HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation
HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation
复制标题
HECT 泛素连接酶 Smurf1 靶向肿瘤抑制因子 ING2 进行泛素化和降解
DOI：
10.1016/j.febslet.2010.05.033
复制
发表时间：
2010-07-16
期刊：
影响因子：
3.5
通讯作者：
Zhang, Lingqiang
中科院分区：
文献类型：
--
作者：
Nie, Jing;Liu, Lin;Zhang, Lingqiang
生长抑制因子2（ING 2）基因编码一个候选的肿瘤抑制因子，在许多肿瘤中经常被降低。然而，ING 2的调节机制，特别是其蛋白质稳定性，仍然不清楚。在这里，我们表明，同源E6 AP羧基末端（HECT）型泛素连接酶Smad泛素化调节因子1（Smurf 1）相互作用，并针对ING 2的多聚泛素化和蛋白酶体降解。有趣的是，Smurf 1中的ING 2结合结构域被映射到催化HECT结构域。此外，ING 2的C-末端PHD结构域是Smurf 1介导的降解所必需的。这项研究首次证明ING 2的稳定性可以通过泛素介导的降解来调节。结构摘要：MINT-7894271：ING 2（uniprotkb：Q9 H160）结合（MI：0407）至Smurf 1（uniprotkb：Q9 HCE 7）通过下拉（MI：0096）MINT-7894319，MINT-7894339：ING 2（uniprotkb：Q9 H160）与Smurf 1发生物理相互作用（MI：0915）（uniprotkb：Q9 HCE 7），抗标签共免疫沉淀法（MI：0007）MINT-7894301：Smurf 1（uniprotkb：Q9 HCE 7）与ING 2发生物理相互作用（MI：0915）（uniprotkb：Q9 H160）抗诱饵免疫共沉淀法（MI：0006）MINT-7894358：ING 1b（uniprotkb：Q9 UK 53 -2）与Smurf 1发生物理相互作用（MI：0915）（uniprotkb：Q9 HCE 7），抗标签共免疫沉淀法（MI：0007）MINT-7894249：ING 2（uniprotkb：Q9 H160）通过抗标签共免疫沉淀（MI：0007）与泛素（uniprotkb：P62988）物理相互作用（MI：0915）（C）2010欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Inhibitor of growth 2 (ING2) gene encodes a candidate tumor suppressor and is frequently reduced in many tumors. However, the mechanisms underlying the regulation of ING2, in particular its protein stability, are 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 ING2 for poly-ubiquitination and proteasomal degradation. Intriguingly, the ING2 binding domain in Smurf1 was mapped to the catalytic HECT domain. Furthermore, the C-terminal PHD domain of ING2 was required for Smurf1-mediated degradation. This study provided the first evidence that the stability of ING2 could be regulated by ubiquitin-mediated degradation.Structured summary:MINT-7894271: ING2 (uniprotkb:Q9H160) binds (MI:0407) to Smurf1 (uniprotkb:Q9HCE7) by pull-down (MI:0096)MINT-7894319, MINT-7894339: ING2 (uniprotkb:Q9H160) physically interacts (MI:0915) with Smurf1 (uniprotkb:Q9HCE7) by anti tag co-immunoprecipitation (MI:0007)MINT-7894301: Smurf1 (uniprotkb:Q9HCE7) physically interacts (MI:0915) with ING2 (uniprotkb: Q9H160) by anti bait co-immunoprecipitation (MI:0006)MINT-7894358: ING1b (uniprotkb:Q9UK53-2) physically interacts (MI:0915) with Smurf1 (uniprotkb: Q9HCE7) by anti tag co-immunoprecipitation (MI:0007)MINT-7894249: ING2 (uniprotkb:Q9H160) physically interacts (MI:0915) with ubiquitin (uniprotkb: P62988) by anti tag co-immunoprecipitation (MI:0007) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.