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Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
- Source :
- BMC Cancer, Vol 21, Iss 1, Pp 1-13 (2021)
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Abstract Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 21
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- BMC Cancer
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.1128292aea34b7d89e20b01b1e11941
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12885-021-08934-x