BINDING OF THE VONHIPPEL-LINDAU TUMOR-SUPPRESSOR PROTEIN TO ELONGIN-BAND ELONGIN-C

Germ-line mutations of the von Hippel-Lindau tumor suppressor gene (VH L) predispose individuals to a variety of human tumors, and somatic mu tations of this gene have been identified in sporadic renal cell carci nomas and cerebellar hemangioblastomas. Two transcriptional elongation factors, Elongin B and C, were shown to bind in vitro and in vivo to a short, colinear region of the VHL protein (pVHL) that is frequently mutated in human tumors. A peptide replica of this region inhibited bi nding of pVHL to Elongin B and C, whereas a point-mutant derivative, c orresponding to a naturally occurring VHL missense mutation, had no ef fect. These results suggest that the tumor suppression function of pVH L may be linked to its ability to bind to Elongin B and C.