The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase

被引:353
作者
Pintard, L [1 ]
Willis, JH
Willems, A
Johnson, JLF
Srayko, M
Kurz, T
Glaser, S
Mains, PE
Tyers, M
Bowerman, B
Peter, M
机构
[1] ETH Honggerberg, Inst Biochem, CH-8093 Zurich, Switzerland
[2] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA
[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med Genet & Microbiol, Toronto, ON M5G 1X5, Canada
[4] Univ Calgary, Genes & Dev Res Grp, Calgary, AB T2N 4N1, Canada
[5] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada
基金
加拿大健康研究院; 美国国家卫生研究院;
关键词
D O I
10.1038/nature01959
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
Many biological processes, such as development and cell cycle progression are tightly controlled by selective ubiquitin-dependent degradation of key substrates. In this pathway, the E3-ligase recognizes the substrate and targets it for degradation by the 26S proteasome. The SCF (Skp1-Cul1-F-box) and ECS (Elongin C-Cul2-SOCS box) complexes are two well-defined cullin-based E3-ligases(1-3). The cullin subunits serve a scaffolding function and interact through their C terminus with the RING-finger-containing protein Hrt1/Roc1/Rbx1, and through their N terminus with Skp1 or Elongin C, respectively. In Caenorhabditis elegans, the ubiquitin-ligase activity of the CUL-3 complex is required for degradation of the microtubule-severing protein MEI-1/katanin at the meiosis-to-mitosis transition(4). However, the molecular composition of this cullin-based E3-ligase is not known. Here we identified the BTB-containing protein MEL-26 as a component required for degradation of MEI-1 in vivo. Importantly, MEL-26 specifically interacts with CUL-3 and MEI-1 in vivo and in vitro, and displays properties of a substrate-specific adaptor. Our results suggest that BTB-containing proteins may generally function as substrate-specific adaptors in Cul3-based E3-ubiquitin ligases.
引用
收藏
页码:311 / 316
页数:6
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