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Supporting data for "The role of deubiquitination in regulating Planar Cell Polarity (PCP) signaling"

posted on 2024-05-21, 01:13 authored by Fangzi Zha

In the previous work, by screening deubiquitinating enzymes (DUBs), we identified two ubiquitin-specific peptidases, USP6 and USP32, for regulating Vangl in planar cell polarity. We found that the ectopic expression of USP6/32 increased Vangl protein level, whereas the depletion of USP6/32 promoted Vangl degradation. Both USP6 and USP32 reduce the polyubiquitination level of Vangl. Loss of USP32 in mice also led to a decrease of Vangl expression and thus an increase of the penetrance of loop tail phenotype in Vangl mutant mice. Moreover, we identified the defect of pancreatic ductal morphogenesis in USP32 KO and Vangl mutant mice. Interestingly, we found that USP32 regulates Vangl in pancreatic cancer. Vangl1 and USP32 are both highly expressed in human pancreatic ductal adenocarcinoma (PDAC) tissues and their expression levels are strongly correlated among various PDAC cell lines. USP32 depletion significantly inhibited the metastasis of PDAC cells to the lung by promoting Vangl degradation, while the similar phenotype could also be observed by reducing Vangl1. Overall, our data reveal a new regulatory mechanism of PCP signaling through USP6 and USP32-mediated Vangl deubiquitination, which play important roles in both development and disease.


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