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Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
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Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

VHL inactivation induces HEF1 and Aurora kinase A

Jianyong Xu1, Huapeng Li, Bo Wang

  • 1Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Journal of the American Society of Nephrology : JASN
|September 25, 2010
PubMed

Insights

Von Hippel-Lindau (VHL) gene inactivation disrupts primary cilia formation in kidney cells by stabilizing hypoxia-inducible factors. This leads to increased cell motility and cyst development, highlighting VHL's crucial role in kidney health.

Area of Science:

  • Cell Biology
  • Oncology
  • Nephrology

Background:

  • Cystic renal diseases are often linked to primary cilia dysfunction.
  • The von Hippel-Lindau (VHL) tumor suppressor gene is critical for primary cilia formation in kidney epithelium.
  • Mechanisms linking VHL inactivation to renal cysts and cancer remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which VHL inactivation affects primary cilia in kidney epithelium.
  • To identify key molecular players involved in VHL-defective renal cystogenesis and cancer.

Main Methods:

  • Investigated the role of VHL, hypoxia-inducible factors (HIFs), HEF1/Cas-L/NEDD9, and Aurora kinase A in VHL-inactivated cells.
  • Examined the impact of VHL inactivation on primary cilia structure and function.
  • Assessed the effect of pathway suppression on cell motility and cilia formation.

Main Results:

  • VHL inactivation stabilizes HIF-1 and HIF-2, inducing HEF1/Cas-L/NEDD9 and Aurora kinase A.
  • Aurora kinase A promotes primary cilia regression via tubulin depolymerization.
  • HEF1/Cas-L/NEDD9 enhances Aurora kinase A's detrimental effect on cilia.
  • Pathway suppression restored primary cilia formation and reduced motility in VHL-defective cells.

Conclusions:

  • VHL acts as a gatekeeper in kidney epithelium, regulating primary cilia integrity.
  • The VHL-HEF1/Aurora kinase A pathway is a key driver of VHL-defective renal cystogenesis and cancer.
  • Targeting this pathway may offer therapeutic strategies for VHL-associated kidney diseases.

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