The ubiquitin ligase RNF38 promotes RUNX1 ubiquitination and enhances RUNX1-mediated suppression of erythroid transcription program
The ubiquitin ligase RNF38 promotes RUNX1 ubiquitination and enhances RUNX1-mediated suppression of erythroid transcription program
复制标题
泛素连接酶 RNF38 促进 RUNX1 泛素化并增强 RUNX1 介导的红细胞转录程序抑制
DOI：
10.1016/j.bbrc.2018.10.006
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发表时间：
2018
影响因子：
3.1
通讯作者：
Goyama Susumu
中科院分区：
文献类型：
--
作者：
Yonezawa Taishi;Takahashi Hirotaka;Shikata Shiori;Sawasaki Tatsuya;Kitamura Toshio;Goyama Susumu
RUNX1是RUNX转录因子中的一员，在造血过程中发挥重要作用。RUNX1的功能通过翻译后修饰（包括磷酸化和泛素化）受到严格控制。我们以前开发了一种基于发光的结合试验（AlphaScreen），以系统地检测RUNX1相互作用的E3泛素连接酶。在这项研究中，我们发现，核泛素连接酶RNF38诱导RUNX1的泛素化。RNF38诱导的RUNX1泛素化不促进RUNX1降解，而是稳定RUNX1蛋白。我们还发现RNF38增强了RUNX1介导的K562细胞中红系主调节因子KLF1的转录抑制。因此，RNF38与RUNX1协同抑制K562细胞的红系分化。因此，我们的研究将RNF38鉴定为一种新型的E3连接酶，其修饰RUNX1功能而不诱导其降解。
RUNX1 is a member of RUNX transcription factors and plays important roles in hematopoiesis. RUNX1 function is under the tight control through posttranslational modifications, including phosphorylation and ubiquitination. We previously developed a luminescence-based binding assay (AlphaScreen) to systematically detect RUNX1-interacting E3 ubiquitin ligases. In this study, we showed that a nuclear ubiquitin ligase RNF38 induced ubiquitination of RUNX1. RNF38-induced RUNX1 ubiquitination did not promote RUNX1 degradation, but rather stabilized RUNX1 protein. We also found that RNF38 enhanced RUNX1-mediated transcriptional repression of the erythroid master regulator KLF1 in K562 cells. Consequently, RNF38 cooperated with RUNX1 to inhibit erythroid differentiation of K562 cells. Thus, our study identified RNF38 as a novel E3 ligase that modifies RUNX1 function without inducing its degradation.