The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1.

The von Hippel-Lindau disease gene (VHL) is the causative gene for most adult renal cancers. However, the mechanism by which VHL protein functions as a renal tumor suppressor remains largely unknown. To identify low occupancy VHL protein partners with potential relevance to renal cancer, we screened a human kidney library ...
against human VHL p30 using a yeast two-hybrid approach. Jade-1 (gene for Apoptosis and Differentiation in Epithelia) encodes a previously uncharacterized 64-kDa protein that interacts strongly with VHL protein and is most highly expressed in kidney. Jade-1 protein is short-lived and contains a candidate destabilizing (PEST) motif and plant homeodomains that are not required for the VHL interaction. Jade-1 is abundant in proximal tubule cells, which are clear-cell renal cancer precursors, and expression increases with differentiation. Jade-1 is expressed in cytoplasm and the nucleus diffusely and in speckles, where it partly colocalizes with VHL. VHL reintroduction into renal cancer cells increases endogenous Jade-1 protein abundance up to 10-fold. Furthermore, VHL increases Jade-1 protein half-life up to 3-fold. Thus, direct protein stabilization is identified as a new VHL function. Moreover, Jade-1 protein represents a novel candidate regulatory factor in VHL-mediated renal tumor suppression.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Blotting, Northern, Blotting, Western, Cell Nucleus, Cytoplasm, Gene Library, Homeodomain Proteins, Humans, Immunohistochemistry, Kidney, Ligases, Microscopy, Fluorescence, Molecular Sequence Data, Plasmids, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Time Factors, Tissue Distribution, Transfection, Tumor Suppressor Proteins, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases, Von Hippel-Lindau Tumor Suppressor Protein
J. Biol. Chem.
Date: Oct. 18, 2002
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