Beta-catenin gets jaded and von Hippel-Lindau is to blame.
Numerous studies have pointed to interactions between the tumor suppressor von Hippel-Lindau (VHL) and the oncogenic Wnt-beta-catenin signaling cascade; however, the mechanism of this crosstalk has remained elusive. Among other roles, VHL can promote the stabilization of Jade-1. Now, recent findings provide compelling evidence that Jade-1 ubiquitylates beta-catenin, leading to its degradation. Thus, the loss of VHL, as seen in clear cell renal cell carcinoma, could lead to tumor formation through beta-catenin de-repression.
Berndt
Jason D
JD
Howard Hughes Medical Institute, Department of Pharmacology and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98109, USA. jdberndt@u.washington.edu
Moon
Randall T
RT
Major
Michael B
MB
D002292:Carcinoma, Renal Cell / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
D018398:Homeodomain Proteins; C469360:JADE1 protein, human; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D051794:Von Hippel-Lindau Tumor Suppressor Protein