USP37 is a SNAI1 deubiquitinase
Zhenna Xiao1,2, Liang Chang1, Jongchan Kim1,3
1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center Houston 77030, Texas, USA.
American Journal of Cancer Research
|January 9, 2020
Summary
USP37 deubiquitinase stabilizes SNAI1, a key factor in tumor metastasis. Inhibiting USP37 reduces SNAI1 levels and cancer cell migration, offering a potential therapeutic strategy against metastasis.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- SNAI1 (Snail family transcriptional repressor 1) is an epithelial-mesenchymal transition (EMT)-inducing transcription factor.
- SNAI1 promotes tumor metastasis, apoptosis resistance, and chemotherapy resistance.
- SNAI1 protein levels are regulated by ubiquitination and proteasomal degradation.
Purpose of the Study:
- To identify deubiquitinases that regulate SNAI1 protein levels.
- To investigate the role of USP37 in SNAI1 stability and cancer cell migration.
Main Methods:
- Co-immunoprecipitation assays to assess protein interactions.
- Western blotting to detect protein levels.
- Ubiquitination assays to analyze protein modification.
- Cell migration assays to evaluate functional impact.
- Expression of wild-type and mutant USP37 in cancer cells.
Main Results:
- USP37 was identified as a deubiquitinase that directly binds and deubiquitinates SNAI1.
- USP37 stabilizes SNAI1 protein by preventing its proteasomal degradation.
- Overexpression of USP37 enhanced cancer cell migration.
- Depletion of USP37 reduced endogenous SNAI1 levels and suppressed cell migration, effects reversible by SNAI1 re-expression.
Conclusions:
- USP37 deubiquitinates and stabilizes SNAI1, promoting cancer cell migration.
- USP37 is a potential therapeutic target for inhibiting tumor metastasis.
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