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

J Biol Chem. 2002 Oct 18;277(42):39887-98. doi: 10.1074/jbc.M205040200. Epub 2002 Aug 6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Gene Library
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / physiology*
  • Humans
  • Immunohistochemistry
  • Kidney / metabolism
  • Ligases / metabolism
  • Ligases / physiology*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Plasmids / metabolism
  • 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

Substances

  • Homeodomain Proteins
  • JADE1 protein, human
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human

Associated data

  • GENBANK/AF520952