Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells
Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells
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DOI：
10.1002/jcp.25841
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发表时间：
2017-12-01
影响因子：
5.6
通讯作者：
Chung, Kwang Chul
中科院分区：
文献类型：
--
作者：
Kim, Dongyeon;Hong, Ahyoung;Chung, Kwang Chul
原癌基因c-Myc在生长控制、分化和细胞凋亡中起关键作用，在包括乳腺癌在内的人类癌症中经常受到影响。泛素特异性蛋白水解酶22(USP22)是脱泛素化酶(DUBS)家族中的一员，它介导组蛋白H_2B和H_2A、端粒重复序列结合因子1和细胞周期蛋白B1等靶蛋白的去泛素化。USP22也是哺乳动物SAGA转录共激活复合体的一个组成部分。在这项研究中，我们探讨了USP22在调节c-Myc稳定性中的功能作用及其在乳腺癌进展中的生理学相关性。我们发现，USP22促进了几种乳腺癌细胞系中c-Myc的去泛素化，导致c-Myc水平增加。与此一致的是，USP22基因敲除会降低c-Myc水平。此外，USP22的过表达刺激乳腺癌细胞的生长和集落形成，并增加c-Myc的致瘤活性。综上所述，本研究显示乳腺癌细胞系中的USP22通过c-Myc去泛素化增加c-Myc的稳定性，而c-Myc去泛素化与乳腺癌的进展密切相关。
The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.