title: 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.
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Patil
authors.forename: Navjotsingh
authors.initials: N
authors.lastname: Pabla
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D000072380:NIMA-Related Kinase 1; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D050257:Tubulin Modulators / Q000494:pharmacology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D050257:Tubulin Modulators; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; C497446:VHL protein, human; D015739:Nocodazole