Tumor Suppression

VHL Gets Jaded in the Kidney

Science's STKE  22 Oct 2002:
Vol. 2002, Issue 155, pp. TW382
DOI: 10.1126/stke.2002.155.TW382


The von Hippel-Lindau (VHL) protein is a tumor suppressor, and mutation of this protein has been linked to various cancers, including renal cancer. Because of its multiple functions, the precise mechanism of VHL action in the kidney has been unresolved. Zhou et al. have identified a VHL-interacting protein called gene for apoptosis and differentiation (Jade-1) through a yeast two-hybrid screen. Jade-1 is highly expressed in human differentiated renal proximal tubules, which are renal cancer precursors. Jade-1 expression decreased in proliferating primary renal cell cultures, suggesting that it may be a negative regulator of cell growth. When overexpressed in cultured cells, VHL and Jade-1 coimmunoprecipitated. Endogenous Jade-1 appeared in the cytoplasm and nucleus, partially colocalizing with VHL. Expression of VHL increased the half-life of Jade-1, in marked contrast to VHL-mediated ubiquitination and destruction of other binding partners. The authors propose that VHL association could alter the phosphorylation of a PEST degradation domain present in JADE to stabilize the protein, and that the two proteins operate together in tumor suppression.

M.I. Zhou, H. Wang, J. J Ross, I. Kuzmin, C. Xu, H. T. Cohen, The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1. J. Biol. Chem. 277, 39887-39898 (2002). [Abstract] [Full Text]