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Updated: May 24, 2026

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model
Published on: April 17, 2026
The ubiquitin-specific protease USP2a enhances tumor progression by targeting cyclin A1 in bladder cancer
Jayoung Kim1, Wun-Jae Kim, Zhiqian Liu
1Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Jayoung.Kim@cshs.org
Abstract:
The deubiquitinating enzyme USP2a has shown oncogenic properties in many cancer types by impairing ubiquitination of FASN, MDM2, MDMX or Aurora A. Aberrant expression of USP2a has been linked to progression of human tumors, particularly prostate cancer. However, little is known about the role of USP2a or its mechanism of action in bladder cancer. Here, we provide evidence that USP2a is an oncoprotein in bladder cancer cells. Enforced expression of USP2a caused enhanced proliferation, invasion, migration and resistance to several chemotherapeutic reagents, while USP2a loss resulted in slower proliferation, greater chemosensitivity and reduced migratory/invasive capability compared with control cells. USP2a, but not a catalytically inactive mutant, enhanced proliferation in immortalized TRT-HU1 normal human bladder epithelial cells. USP2a bound to cyclin A1 and prevented cyclin A1 ubiquitination, leading to accumulation of cyclin A1 by a block in degradation. Enforced expression of wild type USP2a, but not an inactive USP2a mutant, resulted in cyclin A1 accumulation and increased cell proliferation. We conclude that USP2a impairs ubiquitination and stabilizes an important cell cycle regulator, cyclin A1, raising the possibility of USP2a targeting as a therapeutic strategy against bladder tumors in combination with chemotherapy.
Insights
The deubiquitinating enzyme USP2a promotes bladder cancer growth and chemoresistance by stabilizing cyclin A1. Targeting USP2a may offer a new therapeutic strategy for bladder tumors, potentially combined with chemotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The deubiquitinating enzyme USP2a exhibits oncogenic properties in various cancers.
- USP2a dysregulation is linked to tumor progression, especially in prostate cancer.
- The specific role and mechanism of USP2a in bladder cancer remain largely unexplored.
Purpose of the Study:
- To investigate the role of USP2a as an oncoprotein in bladder cancer.
- To elucidate the underlying molecular mechanism of USP2a action in bladder cancer cells.
Main Methods:
- Enforced expression and loss of USP2a in bladder cancer cells.
- Assessment of proliferation, invasion, and migration.
- Chemosensitivity assays.
- Analysis of USP2a interaction with cyclin A1 and its ubiquitination status.
Main Results:
- USP2a overexpression enhanced bladder cancer cell proliferation, invasion, migration, and chemoresistance.
- USP2a depletion reduced these aggressive phenotypes and increased chemosensitivity.
- USP2a stabilized cyclin A1 by inhibiting its ubiquitination and degradation, leading to increased proliferation.
Conclusions:
- USP2a functions as an oncoprotein in bladder cancer.
- USP2a promotes bladder cancer progression by stabilizing cyclin A1.
- Targeting USP2a presents a potential therapeutic strategy for bladder cancer, possibly in combination with chemotherapy.
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