Galan J M, Peter M
Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, 1066 Epalinges/VD, Switzerland.
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9124-9. doi: 10.1073/pnas.96.16.9124.
Ubiquitin-dependent degradation of regulatory proteins controls many cellular processes, including cell cycle progression, morphogenesis, and signal transduction. Skp1p-cullin-F-box protein (SCF) complexes are ubiquitin ligases composed of a core complex including Skp1p, Cdc53p, one of multiple F-box proteins that are thought to provide substrate specificity to the complex, and the ubiquitin-conjugating enzyme, Cdc34p. It is not understood how SCF complexes are regulated and how physiological conditions alter their levels. Here we show that three F-box proteins, Grr1p, Cdc4p, and Met30p, are unstable components of the SCF, and are themselves degraded in a ubiquitin- and proteasome-dependent manner in vivo. Ubiquitination requires all the core components of the SCF and an intact F-box, suggesting that ubiquitination occurs within the SCF complex by an autocatalytic mechanism. Cdc4p and Grr1p are intrinsically unstable, and their steady-state levels did not fluctuate through the cell cycle. Taken together, our results suggest that ubiquitin-dependent degradation of F-box proteins allows rapid switching among multiple SCF complexes, thereby enabling cells to adapt quickly to changing physiological conditions and progression through different phases of the cell cycle.
泛素依赖的调节蛋白降解控制着许多细胞过程，包括细胞周期进程、形态发生和信号转导。Skp1p-库林-F盒蛋白（SCF）复合物是泛素连接酶，由一个核心复合物组成，该核心复合物包括Skp1p、Cdc53p、多种F盒蛋白之一（据认为这些F盒蛋白为复合物提供底物特异性）以及泛素结合酶Cdc34p。目前尚不清楚SCF复合物是如何被调节的，以及生理条件如何改变它们的水平。在这里，我们表明三种F盒蛋白Grr1p、Cdc4p和Met30p是SCF的不稳定成分，并且它们自身在体内以泛素和蛋白酶体依赖的方式被降解。泛素化需要SCF的所有核心成分和完整的F盒，这表明泛素化通过自催化机制在SCF复合物内发生。Cdc4p和Grr1p本质上是不稳定的，它们的稳态水平在细胞周期中没有波动。综上所述，我们的结果表明，F盒蛋白的泛素依赖降解允许在多个SCF复合物之间快速切换，从而使细胞能够快速适应不断变化的生理条件并在细胞周期的不同阶段进行进程。
