INHIBITION OF TRANSCRIPTION ELONGATION BY THE VHL TUMOR-SUPPRESSOR PROTEIN

Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL ) predispose individuals to a variety of tumors, including renal carci noma, hemangioblastoma of the central nervous system, and pheochromocy toma. Here, a cellular transcription factor, Elongin (SIII), is identi fied as a functional target of the VHL protein. Elongin (SIII) is a he terotrimer consisting of a transcriptionally active subunit (A) and tw o regulatory subunits (B and C) that activate transcription elongation by RNA polymerase II. The VHL protein was shown to bind tightly and s pecifically to the Elongin B and C subunits and to inhibit Elongin (SI II) transcriptional activity in vitro. These findings reveal a potenti ally important transcriptional regulatory network in which the VHL pro tein may play a key role.