OTUB1 对 MYC 的去泛素化作用促进 HK2 介导的糖酵解和乳腺癌发生。
Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis.
机构信息
Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, P.R. China.
出版信息
Cell Death Differ. 2022 Sep;29(9):1864-1873. doi: 10.1038/s41418-022-00971-8. Epub 2022 Mar 16.
Abstract
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.
摘要
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，MYC 在乳腺癌中的去泛素化机制尚不清楚。在这里，我们报告 OTUB1 负责 MYC 的去泛素化。OTUB1 可以直接在 K323 位点对 MYC 进行去泛素化，从而阻止 MYC 蛋白的降解。此外，在 OTUB1 敲除小鼠中也证实了 OTUB1 介导的 MYC 蛋白稳定性。OTUB1 稳定的 MYC 促进其转录活性，并诱导 HK2 的表达，从而增强有氧糖酵解。因此，OTUB1 通过阻止 MYC 蛋白降解，在体内和体外促进乳腺癌的发生。总之，我们的数据确定 OTUB1 是 MYC 蛋白降解的一种新的去泛素化酶，为乳腺癌的治疗提供了一个潜在的靶点。
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