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

Science  23 Apr 1999:
Vol. 284, Issue 5414, pp. 657-661
DOI: 10.1126/science.284.5414.657

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Abstract

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.

  • * To whom correspondence should be addressed. E-mail: conawayj{at}omrf.ouhsc.edu

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