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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.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We thank Dr. William Kaelin at Harvard Medical School for providing the HA-VHL-pRc-CMV plasmid and Dr. Celeste Simon at University of Pennsylvania for RCC4 cells. The study was supported in part by research grants from the National Institutes of Health and Department of Veteran’s Affairs.
