Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells

Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung

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90 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3664-3676
Number of pages13
JournalJournal of Cellular Physiology
Issue number12
Publication statusPublished - 2017 Dec

Bibliographical note

Funding Information:
The authors thank B.S. Atanassov, K.H. Baek, D. A. Sinclair, H.D. Youn, I.K. Chung, B.E. Clurman, and H.S. Park for providing plasmids and J. Choi, C. Lee, and N.H. Cho for providing human breast cancer cell lines. The article was supported by grants from National Research Foundation of Korea (NRF), grant number: 2014M3C7A1064545 and 2015R1A2A2A01003080 to K.C.C.; Korea Health Industry Development Institute (KHIDI), grant number: HI14C0093 to K.C.C.; Yonsei University Future-leading Research Initiative of 2015, grant number: 2015-22-0055 to K.C.C. The authors declare that they have no competing interests.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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