Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase

T. Kamura, D. M. Koepp, M. N. Conrad, D. Skowyra, R. J. Moreland, O. Iliopoulos, W. S. Lane, W. G. Kaelin, S. J. Elledge, R. C. Conaway, J. W. Harper, J. W. Conaway

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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 SCF(Cdc4) 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.

Original languageEnglish (US)
Pages (from-to)657-661
Number of pages5
JournalScience
Volume284
Issue number5414
DOIs
StatePublished - Apr 23 1999

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Kamura, T., Koepp, D. M., Conrad, M. N., Skowyra, D., Moreland, R. J., Iliopoulos, O., Lane, W. S., Kaelin, W. G., Elledge, S. J., Conaway, R. C., Harper, J. W., & Conaway, J. W. (1999). Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science, 284(5414), 657-661. https://doi.org/10.1126/science.284.5414.657