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Updated: Feb 19, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
USP51 promotes deubiquitination and stabilization of ZEB1
Zhicheng Zhou1, Peijing Zhang1, Xiaoyu Hu1
1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer CenterHouston, TX 77030, USA.
Abstract:
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.
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