TY - JOUR
T1 - USP51 promotes deubiquitination and stabilization of ZEB1
AU - Zhou, Zhicheng
AU - Zhang, Peijing
AU - Hu, Xiaoyu
AU - Kim, Jongchan
AU - Yao, Fan
AU - Xiao, Zhenna
AU - Zeng, Liyong
AU - Chang, Liang
AU - Sun, Yutong
AU - Ma, Li
N1 - Funding Information:
Drs. Zhendong Xiao, Yilei Zhang, Hyemin Lee, and Chao Wang (MD Anderson Cancer Center) for reagents and technical assistance; and members of the Ma Lab for discussion. We thank MD Anderson’s shRNA and ORFeome Core for technical support. L.M. is supported by US National Institutes of Health grants R01CA166051 and R01CA181029, a Cancer Prevention and Research Institute of Texas grant RP150319, and a Stand Up To Cancer Innovative Research Grant.
PY - 2017
Y1 - 2017
N2 - ZEB1 is a transcription factor that induces epithelial-mesenchymal transition, tumor metastasis, and therapy resistance. ZEB1 protein is subject to ubiquitination and degradation, but the mechanism by which ZEB1 is stabilized in cells remains unclear. By screening a human deubiquitinase library, we identified USP51 as a deubiquitinase that binds, deubiquitinates, and stabilizes ZEB1. Depletion of USP51 in mesenchymal-like breast cancer cells led to downregulation of ZEB1 protein and mesenchymal markers, upregulation of E-cadherin, and inhibition of cell invasion. Conversely, overexpression of USP51 in epithelial cells resulted in upregulation of ZEB1 and mesenchymal markers. In addition, USP51 is able to regulate the expression of ZEB1 target genes. Importantly, USP51 is overexpressed in breast cancer patients and correlates with poor survival. Taken together, our findings suggest that USP51 is a ZEB1 deubiquitinase that may serve as an alternative pathway for targeting the cancer-promoting transcriptional factor ZEB1.
AB - ZEB1 is a transcription factor that induces epithelial-mesenchymal transition, tumor metastasis, and therapy resistance. ZEB1 protein is subject to ubiquitination and degradation, but the mechanism by which ZEB1 is stabilized in cells remains unclear. By screening a human deubiquitinase library, we identified USP51 as a deubiquitinase that binds, deubiquitinates, and stabilizes ZEB1. Depletion of USP51 in mesenchymal-like breast cancer cells led to downregulation of ZEB1 protein and mesenchymal markers, upregulation of E-cadherin, and inhibition of cell invasion. Conversely, overexpression of USP51 in epithelial cells resulted in upregulation of ZEB1 and mesenchymal markers. In addition, USP51 is able to regulate the expression of ZEB1 target genes. Importantly, USP51 is overexpressed in breast cancer patients and correlates with poor survival. Taken together, our findings suggest that USP51 is a ZEB1 deubiquitinase that may serve as an alternative pathway for targeting the cancer-promoting transcriptional factor ZEB1.
KW - Deubiquitinase
KW - USP51
KW - ZEB1
UR - http://www.scopus.com/inward/record.url?scp=85032505094&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032505094&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:85032505094
SN - 2156-6976
VL - 7
SP - 2020
EP - 2031
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
IS - 10
ER -