AI Article Synopsis
- β-catenin is a crucial part of the WNT signaling pathway and is usually regulated through a process called ubiquitin-dependent proteolysis.
- USP4 was identified as a deubiquitinating enzyme that stabilizes β-catenin and boosts its ability to promote transcription.
- Increased levels of USP4 and β-catenin were found in colon cancer tissues, suggesting that targeting USP4 could be a promising strategy for cancer treatment.
Article Abstract
β-catenin is a key signal transducer in the canonical WNT pathway and is negatively regulated by ubiquitin-dependent proteolysis. Through screening of various deubiquitinating enzymes (DUBs), we identified ubiquitin specific protease 4 (USP4) as a candidate for β-catenin-specific DUB. The effects of USP4 overexpression or knockdown suggested that USP4 positively controls the stability of β-catenin and enhances β-catenin-regulated transcription. Domain mapping results revealed that the C-terminal catalytic domain is responsible for β-catenin binding and nuclear transport. Examination of colon cancer tissues from patients revealed a correlation between elevated expression levels of USP4 and β-catenin. Consistent with this correlation, USP4 knockdown in HCT116, a colon cancer cell line, reduced invasion and migration activity. These observations indicate that USP4 acts as a positive regulator of the WNT/β-catenin pathway by deubiquitination and facilitates nuclear localization of β-catenin. Therefore, we propose that USP4 is a potential target for anti-cancer therapeutics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528720 | PMC |
| http://dx.doi.org/10.1016/j.molonc.2015.06.006 | DOI Listing |
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