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

doi:10.1126/science.284.5414.657

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

Genetics, Cell Biology and Development (CBS)

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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 language	English (US)
Pages (from-to)	657-661
Number of pages	5
Journal	Science
Volume	284
Issue number	5414
DOIs	https://doi.org/10.1126/science.284.5414.657
State	Published - Apr 23 1999

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

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.",

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AU - Kamura, T.

AU - Koepp, D. M.

AU - Conrad, M. N.

AU - Skowyra, D.

AU - Moreland, R. J.

AU - Iliopoulos, O.

AU - Lane, W. S.

AU - Kaelin, W. G.

AU - Elledge, S. J.

AU - Conaway, R. C.

AU - Harper, J. W.

AU - Conaway, J. W.

PY - 1999/4/23

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N2 - 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.

AB - 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.

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ER -

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

Abstract

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