Letter abstract
Nature Cell Biology 10, 1208 - 1216 (2008)
Published online: 21 September 2008 | doi:10.1038/ncb1781
Jade-1 inhibits Wnt signalling by ubiquitylating 
-catenin and mediates Wnt pathway inhibition by pVHL
Vipul C. Chitalia1, Rebecca L. Foy1, Markus M. Bachschmid2, Liling Zeng1, Maria V. Panchenko1, Mina I. Zhou1, Ajit Bharti3, David C. Seldin4, Stewart H. Lecker5, Isabel Dominguez4 & Herbert T. Cohen1,4
The von Hippel–Lindau protein pVHL suppresses renal tumorigenesis in part by promoting the degradation of hypoxia-inducible HIF-
transcription factors1; additional mechanisms have been proposed2. pVHL also stabilizes the plant homeodomain protein Jade-1, which is a candidate renal tumour suppressor that may correlate with renal cancer risk3, 4, 5. Here we show that Jade-1 binds the oncoprotein 
-catenin in Wnt-responsive fashion. Moreover, Jade-1 destabilizes wild-type -catenin but not a cancer-causing form of -catenin. Whereas the well-established -catenin E3 ubiquitin ligase component -TrCP ubiquitylates only phosphorylated -catenin6, Jade-1 ubiquitylates both phosphorylated and non-phosphorylated -catenin and therefore regulates canonical Wnt signalling in both Wnt-off and Wnt-on phases. Thus, the different characteristics of -TrCP and Jade-1 may ensure optimal Wnt pathway regulation. Furthermore, pVHL downregulates -catenin in a Jade-1-dependent manner and inhibits Wnt signalling, supporting a role for Jade-1 and Wnt signalling in renal tumorigenesis. The pVHL tumour suppressor and the Wnt tumorigenesis pathway are therefore directly linked through Jade-1.
- Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
- Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
- Molecular Stress Response Unit, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
- Hematology–Oncology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
- Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02118, USA.
Correspondence to: Herbert T. Cohen1,4 e-mail: htcohen@bu.edu
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