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

被引:660
作者
Kamura, T
Koepp, DM
Conrad, MN
Skowyra, D
Moreland, RJ
Iliopoulos, O
Lane, WS
Kaelin, WG
Elledge, SJ
Conaway, RC
Harper, JW
Conway, JW
机构
[1] Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA
[2] Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA
[3] Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA
[4] Baylor Coll Med, Verna & Marrs McLean Dept Biochem, Houston, TX 77030 USA
[5] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[6] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
[8] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
[9] Harvard Univ, Harvard Microchem Facil, Cambridge, MA 02138 USA
[10] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA
关键词
D O I
10.1126/science.284.5414.657
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 G(1) to S cell cycle transition. These findings provide a further Link between VHL and the cellular ubiquitination machinery.
引用
收藏
页码:657 / 661
页数:5
相关论文
共 31 条
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