Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis
Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis
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DOI：
10.1038/s41418-022-00971-8
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发表时间：
2022-03-16
影响因子：
12.4
通讯作者：
Yu, Zhenhai
中科院分区：
文献类型：
--
作者：
Han, Xue;Ren, Chune;Yu, Zhenhai
MYC作为一种转录因子在乳腺癌的进展中起着至关重要的作用。然而，乳腺癌中MYC去泛素化的潜在机制尚未明确。在这里，我们报告OTUB 1负责MYC去泛素化。OTUB 1可直接在K323位点去泛素化MYC，从而阻断MYC蛋白的降解。此外，OTUB 1介导的MYC蛋白稳定性也在OTUB 1敲除小鼠中得到证实。OTUB 1稳定的MYC促进其转录活性并诱导HK2表达，这导致有氧糖酵解增强。因此，OTUB 1通过阻断MYC蛋白降解促进体内和体外乳腺肿瘤发生。综上所述，我们的数据确定OTUB 1作为一种新的MYC蛋白降解的去泛素化酶，这为乳腺癌治疗提供了一个潜在的靶点。
MYC as a transcriptional factor plays a crucial role in breast cancer progression. However, the mechanisms underlying MYC deubiquitination in breast cancer are not well defined. Here, we report that OTUB1 is responsible for MYC deubiquitination. OTUB1 could directly deubiquitinate MYC at K323 site, which blocks MYC protein degradation. Moreover, OTUB1 mediated MYC protein stability is also confirmed in OTUB1-knockout mice. Stabilized MYC by OTUB1 promotes its transcriptional activity and induces HK2 expression, which leads to enhance aerobic glycolysis. Therefore, OTUB1 promotes breast tumorigenesis in vivo and in vitro via blocking MYC protein degradation. Taken together, our data identify OTUB1 as a new deubiquitination enzyme for MYC protein degradation, which provides a potential target for breast cancer treatment.