AB175. The first large-scale study of VHL gene mutation spectrum and genotype-phenotype correlationship of VHL disease in China

© Translational Andrology and Urology. All rights reserved. Transl Androl Urol, 2015;4(S1) www.amepc.org/tau pVHL, HIF-2a and Glut-1 was obviously lower than constant cell line; the half-time of missense mutant pVHL was shorter than the wild-type one(t1/2 mut =1.5 h vs. t1/2 wt =4 h). After treated with celastrol, the half-time of mutant pVHL increased to 3 h. Co-IP indicated that celastrol increased the interaction between mutant pVHL and HSP70, and decreased the HSP90 binding. Conclusions: The mechanism of VHL gene missense mutation in tumorigenesis is not loss of protein intrinsic function, but the rapid degradation of mutant pVHL. Therapeutic modification of missense pVHL degradation may provide new strategies for treatment of RCC. Celastrol protects missense pVHL mutants by regulating the proteinprotein-interaction in molecular chaperone system, and may develop into a potential new drug for RCC.