Nek1 phosphorylates von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization

Mallikarjun Patil, Navjotsingh Pabla, Shuang Huang, Zheng Dong

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Loss of function in either VHL or Nek1 leads to cyst formation in tissues, especially in kidneys. Whether there is a connection between pVHL and Nek1 regulation is unknown. Here, we report that the VHL protein (pVHL) may be a substrate of Nek1. While Nek1 can phosphorylate pVHL at multiple sites, the phosphorylation at serine-168 results in pVHL degradation. Nek1-mediated phosphorylation of pVHL does not significantly affect hypoxia-inducible factors (HIF), a known target of pVHL. However, non-phosphorylable pVHL reconstituted in VHL-deficient cells induces more stable cilia than wild-type VHL during serum stimulation and Nocodazole treatment. The results suggest a possible regulation of pVHL by Nek1 that may contribute to ciliary homeostasis and cystogenesis.

Original languageEnglish (US)
Pages (from-to)166-171
Number of pages6
JournalCell Cycle
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Phosphorylation
Nocodazole
Cilia
Serine
Cysts
Neoplasms
Homeostasis
Kidney
Serum
Proteins
Hypoxia

Keywords

  • Cilium
  • Hypoxia-inducible factor
  • Nek1
  • Phosphorylation
  • VHL

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Nek1 phosphorylates von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization. / Patil, Mallikarjun; Pabla, Navjotsingh; Huang, Shuang; Dong, Zheng.

In: Cell Cycle, Vol. 12, No. 1, 01.01.2013, p. 166-171.

Research output: Contribution to journalArticle

Patil, Mallikarjun ; Pabla, Navjotsingh ; Huang, Shuang ; Dong, Zheng. / Nek1 phosphorylates von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization. In: Cell Cycle. 2013 ; Vol. 12, No. 1. pp. 166-171.
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