RSUME enhances angiogenesis by promoting the loss of function of VHL mutants

TEDESCO, L; CÁRDENAS FIGUEROA, C; ELGUERO, B; ERDOCIA, M; ARZT, E; GONILSKI PACIN, D; FUERTES, M

Ciudad Autónoma de Buenos Aires

Simposio; Frontiers in biosciences 3; 2018

Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET - Partner Institute of the Max Planck Society

Von Hippel?Lindau (VHL) isan inherited disorder caused by mutations inVHL protein and characterized by thedevelopment of high vascularized solid tumors,such as Hemangioblastomas of the centralnervous system and retina, renal clear-cellcarcinomas (RCC) and Pheocromocytoma. VHLtumorsuppressor-containing E3 ubiquitin ligasecomplex (ECV) drives the degradation ofhypoxia-inducible transcription factors (HIFs) innormoxia. In spite of type 1 VHL mutations, inType 2 VHL mutations a complete VHL protein isproduced but it has an abnormal function leadingto HIFs deregulation. RSUME (RWD domaincontainingprotein SUMO Enhancer) is inducedby cellular stress, such as hypoxia (HPX) andleads HIF stabilization. Previously we haveshown that RSUME is highly expressed intissues prone to tumor development in thecontext of VHL disesase.OBJETIVES: Our aim were a) investigate theaction of RSUME on Vhl type 2 phenotypepotenciation, b) dilucidate RSUME impact ontype 2 VHL-related tumor angiogenesis and c)develop a mouse model to study this pathology.