KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation
Autor: | Mu Ling, Yuxuan Chen, Zhao Dawei, Zhang Kun, Weiming Ge, Wenkun Zhuo, Yusheng Guo |
---|---|
Rok vydání: | 2021 |
Předmět: |
Leiomyosarcoma
Proteasome Endopeptidase Complex Chromosomal Proteins Non-Histone Cell Biophysics Kinesins Proto-Oncogene Mas Biochemistry Ubiquitin Downregulation and upregulation Cell Line Tumor medicine Humans Poly-ADP-Ribose Binding Proteins Molecular Biology Cell Proliferation Oncogene Proteins Gene knockdown biology KIF15 Protein Stability Cell growth Chemistry Ubiquitination Cell Biology Up-Regulation Cell biology Gene Expression Regulation Neoplastic stomatognathic diseases medicine.anatomical_structure Cell culture Proteolysis biology.protein Kinesin Ubiquitin-Specific Proteases Protein Binding |
Zdroj: | Biochemical and Biophysical Research Communications. 570:117-124 |
ISSN: | 0006-291X |
Popis: | Kinesin Family Member 15 (KIF15) is a plus end-directed microtubule motor, which exerts complex regulations in cancer biology. This study aimed to explore the functional role of KIF15 in leiomyosarcoma (LMS). Bioinformatic analysis was carried out using data from The Cancer Genome Atlas (TCGA)-Sarcoma (SARC). LMS cell lines SK-UT-1 and SK-LMS-1 were used as in vitro cell models. Results showed that LMS patients with high KIF15 expression had significantly worse survival than the low KIF15 expression counterparts. KIF15 knockdown slowed, while KIF15 overexpression increased the proliferation of SK-UT-1 and SK-LMS-1 cells. Co-IP assay confirmed mutual interaction between endogenous KIF15 and DEK (encoded by DEK proto-oncogene). KIF15 knockdown facilitated DEK degradation, while KIF15 overexpression slowed DEK degradation. In ubiquitination assay, a significant increase in DEK polyubiquitylation was observed when KIF15 expression was suppressed. USP15 physically interacted with both DEK and KIF15 in the cells. USP15 knockdown decreased DEK protein stability and canceled KIF15-mediated DEK stabilization. USP15 overexpression enhanced DEK stability, the effect of which was impaired by KIF15 knockdown. USP15 overexpression reduced DEK polyubiquitination. USP15 knockdown increased DEK polyubiquitination and canceled the effect of KIF15 overexpression on reducing DEK polyubiquitination. DEK overexpression enhanced the proliferation of SK-UT-1 and SK-LMS-1 cells. DEK knockdown decreased cell proliferation and canceled the effect of KIF15 overexpression on cell proliferation. In conclusion, this study revealed a novel mechanism that KIF15 enhances LMS cell proliferation via preventing DEK protein from degradation by increasing USP15 mediated deubiquitylation. |
Databáze: | OpenAIRE |
Externí odkaz: |