Individuals harboring germline mutations in the tumor suppressor gene von Hippel-Lindau (VHL) exhibit an increased susceptibility to a variety of tumors including renal carcinoma, hemangio-blastoma of the central nervous system and pheochromo-cytoma. The Elongin (SIII) complex has been identified as the functional target of the VHL protein. Elongin (SIII) is a heterotrimer composed of a transcriptional active subunit designated Elongin A and two regulatory subunits designated Elongin B and Elongin C. VHL functions by binding to the Elongin B and C subunits, inhibiting the transcriptional efficacy of the Elongin (SIII) complex. The VHL protein migrates with an apparent molecular weight of 38 kDa. The Elongin A subunit is 773 amino acids in length and has an apparent molecular weight of 110 kDa, while Elongin B and C are 18 kDa and 15 kDa proteins, respectively.
