Furukawa Manabu, He Yizhou Joseph, Borchers Christoph, Xiong Yue
Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, NC 27599-7295, USA.
Nat Cell Biol. 2003 Nov;5(11):1001-7. doi: 10.1038/ncb1056. Epub 2003 Oct 5.
The concentrations and functions of many cellular proteins are regulated by the ubiquitin pathway. Cullin family proteins bind with the RING-finger protein Roc1 to recruit the ubiquitin-conjugating enzyme (E2) to the ubiquitin ligase complex (E3). Cul1 and Cul7, but not other cullins, bind to an adaptor protein, Skp1. Cul1 associates with one of many F-box proteins through Skp1 to assemble various SCF-Roc1 E3 ligases that each selectively ubiquitinate one or more specific substrates. Here, we show that Cul3, but not other cullins, binds directly to multiple BTB domains through a conserved amino-terminal domain. In vitro, Cul3 promoted ubiquitination of Caenorhabditis elegans MEI-1, a katanin-like protein whose degradation requires the function of both Cul3 and BTB protein MEL-26. We suggest that in vivo there exists a potentially large number of BCR3 (BTB-Cul3-Roc1) E3 ubiquitin ligases.
许多细胞蛋白质的浓度和功能受泛素途径调控。Cullin家族蛋白与RING指蛋白Roc1结合，将泛素结合酶（E2）招募到泛素连接酶复合体（E3）。Cul1和Cul7而非其他Cullin蛋白与衔接蛋白Skp1结合。Cul1通过Skp1与众多F盒蛋白之一结合，组装各种SCF-Roc1 E3连接酶，每种连接酶选择性地使一种或多种特定底物泛素化。在此，我们表明，Cul3而非其他Cullin蛋白通过一个保守的氨基末端结构域直接与多个BTB结构域结合。在体外，Cul3促进了秀丽隐杆线虫MEI-1的泛素化，MEI-1是一种类似katanin的蛋白，其降解需要Cul3和BTB蛋白MEL-26的功能。我们认为，体内可能存在大量BCR3（BTB-Cul3-Roc1）E3泛素连接酶。
