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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cilia / drug effects
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HEK293 Cells
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Humans
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Molecular Sequence Data
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Mutation
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NIMA-Related Kinase 1
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Nocodazole / pharmacology
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Phosphorylation
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Proteasome Endopeptidase Complex / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Transfection
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Tubulin Modulators / pharmacology
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Von Hippel-Lindau Tumor Suppressor Protein / genetics
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Von Hippel-Lindau Tumor Suppressor Protein / metabolism*
Substances
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Cell Cycle Proteins
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Tubulin Modulators
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Von Hippel-Lindau Tumor Suppressor Protein
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NEK1 protein, human
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NIMA-Related Kinase 1
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Protein Serine-Threonine Kinases
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Proteasome Endopeptidase Complex
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VHL protein, human
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Nocodazole