Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis |
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| Authors: | Arun Pandian Chandrasekaran Sang Hyeon Woo Neha Sarodaya Byung Ho Rhie Apoorvi Tyagi Soumyadip Das Bharathi Suresh Na Re Ko Seung Jun Oh Kye-Seong Kim Suresh Ramakrishna |
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| Affiliation: | 1.Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea; (A.P.C.); (S.H.W.); (N.S.); (B.H.R.); (A.T.); (S.D.); (B.S.);2.Biomedical Research Center, Asan Institute for Life Sciences, Seoul 05505, Korea;3.Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;4.College of Medicine, Hanyang University, Seoul 04763, Korea |
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| Abstract: | Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A. |
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| Keywords: | apoptosis cell cycle deubiquitinase oncogenic transformation proteolysis tumor model ubiquitination |
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