Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells.
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.
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Dongyeon
D
Kim
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Ahyoung
A
Hong
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Hye In
HI
Park
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Woo Hyun
WH
Shin
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Lang
L
Yoo
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Seo Jeong
SJ
Jeon
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Kwang Chul
KC
Chung
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006207:Half-Life; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology; D006801:Humans; D061986:MCF-7 Cells; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D059748:Proteolysis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination
C000715470:MAS1 protein, human; C489427:MYC protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human
DUB; USP22; breast cancer; c-Myc; deubiquitination; proteolysis