2. Academic Validation
  3. VHL regulates NEK1 via both HIF-2α pathway and ubiquitin-proteasome pathway in renal cancer cell

VHL regulates NEK1 via both HIF-2α pathway and ubiquitin-proteasome pathway in renal cancer cell

  • Biochem Biophys Res Commun. 2019 Feb 12;509(3):797-802. doi: 10.1016/j.bbrc.2019.01.001.
Guang Chen 1,  Jun Zhou 2,  Jie Chen 3,  Jin Zhu 4,  Shuang-Chun Liu 4,  Xiao-Fei Ding 5,  Qiang Zhang 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Medicine, Taizhou University, China; Institute of Tumor, Taizhou University, China.
  • 2 Institute of Tumor, Taizhou University, China.
  • 3 Laboratory for Biological Medicine, School of Medicine, Taizhou University, China.
  • 4 Department of Surgical Oncology, Taizhou Municipal Hospital, Taizhou University, Taizhou, Zhejiang, 318000, China.
  • 5 Laboratory for Biological Medicine, School of Medicine, Taizhou University, China. Electronic address: dxfei@tzc.edu.cn.
  • 6 Department of Surgical Oncology, Taizhou Municipal Hospital, Taizhou University, Taizhou, Zhejiang, 318000, China. Electronic address: z-q2007@163.com.
PMID: 30635121 DOI: 10.1016/j.bbrc.2019.01.001
Abstract

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.

Keywords

HIF-2α; NEK1; Renal cancer; Ubiquitin; VHL.

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