VHL regulates NEK1 via both HIF-2α pathway and ubiquitin-proteasome pathway in renal cancer cell
| Autor: | Shuang-Chun Liu, Qiang Zhang, Jun Zhou, Xiao-Fei Ding, Jie Chen, Guang Chen, Jin Zhu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex endocrine system diseases Biophysics Protein degradation urologic and male genital diseases Biochemistry law.invention Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Ubiquitin law Cell Line Tumor Basic Helix-Loop-Helix Transcription Factors Animals Humans neoplasms Molecular Biology Gene knockdown biology Chemistry Kinase Cell Biology female genital diseases and pregnancy complications Kidney Neoplasms 030104 developmental biology NIMA-Related Kinase 1 Proteasome Von Hippel-Lindau Tumor Suppressor Protein 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Suppressor Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 509(3) |
| ISSN: | 1090-2104 |
| Popis: | Both Von Hippel-Lindau tumor suppressor (VHL) and Never-in-mitosis A (NIMA)-related kinase 1 (NEK1) are involved in primary cilium formation, but whether VHL could regulate NEK1 is unknown. Here, we demonstrated that renal cancer cells Caki-1 and ACHN with wild-type VHL expressed lower level of NEK1 than that of VHL-defective cells including 786-O, 769-P and A498 cells. VHL-overexpression down-regulated NEK1 in 769-P cells, while VHL-knockdown up-regulated NEK1 in Caki-1 cells. In addition, we found the hypoxia response element (HRE) in the promoter sequence of NEK1 and hypoxia induced NEK1 expression both in vitro and in vivo. HIF-2α knockdown blocked hypoxia induced NEK1 upregulation instead of HIF-1α, which indicates that NEK1 may be a new target of HIF-2α. Moreover, we confirmed the association between VHL and NEK1 in Caki-1 cell, then showed VHL promoted NEK1 protein degradation and ubiquitination. In conclusion, our findings showed VHL regulates NEK1 via both HIF-2α pathway and ubiquitin-proteasome pathway in renal cancer cells. |
| Databáze: | OpenAIRE |
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