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The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis

A R Schoenfeld1, T Parris, A Eisenberger

  • 1Department of Microbiology and Immunology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Oncogene
|December 29, 2000
PubMed

Insights

Loss of the von Hippel-Lindau (VHL) gene in renal cells causes UV-induced apoptosis by degrading cell cycle inhibitors. Restoring VHL function protects cells from UV damage and promotes survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Von Hippel-Lindau (VHL) disease is a familial cancer syndrome linked to VHL tumor suppressor gene inactivation.
  • VHL gene loss is common in sporadic renal cell carcinoma (RCC).
  • VHL protein is known to protect cells against serum withdrawal and glucose deprivation.

Purpose of the Study:

  • To investigate the effect of UV irradiation on renal carcinoma cells with and without VHL gene function.
  • To elucidate the molecular mechanisms underlying VHL's role in cellular response to UV damage.

Main Methods:

  • Comparison of UV irradiation effects on VHL-negative (786-O) and VHL-positive (reconstituted) renal carcinoma cells.
  • Analysis of apoptosis markers, cell cycle regulators (p53, Bax, p21, p27), and anti-apoptotic proteins (Bcl-2, Bcl-xL).
  • Assessment of cell cycle progression (S phase) and protein degradation pathways (proteasome).

Main Results:

  • VHL-negative cells underwent apoptosis after UV irradiation, while VHL-positive cells were protected.
  • UV treatment caused proteasome-dependent degradation of p21 and p27 in VHL-negative cells, but not in VHL-positive cells.
  • VHL-positive cells showed elevated anti-apoptotic proteins (Bcl-2, Bcl-xL) and stable p21/p27 levels, preventing UV-induced apoptosis and hyperproliferation.

Conclusions:

  • Loss of VHL function promotes UV-induced apoptosis in renal carcinoma cells.
  • The degradation of p21 and p27 in VHL-deficient cells leads to a hyperproliferative state, ultimately resulting in apoptosis.
  • These findings suggest that VHL loss creates selective pressure favoring the survival of cells that can evade apoptosis, contributing to tumorigenesis.

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