Rbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase

✍ Scribed by Kamura, T.

• Book ID: 115459219
• Publisher: American Association for the Advancement of Science
• Year: 1999
• Tongue: English
• Weight: 431 KB
• Volume: 284
• Category: Article
• ISSN: 0036-8075
• DOI: 10.1126/science.284.5414.657

✦ Synopsis

The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.