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

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.

SUBMITTER: Patil M

PROVIDER: S-EPMC3570507 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Patil Mallikarjun M Pabla Navjotsingh N Huang Shuang S Dong Zheng Z

Cell cycle (Georgetown, Tex.) 20121219 1

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-p ...[more]

PMID: 23255108

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