Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism
Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism
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DOI：
10.1073/pnas.96.16.9124
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发表时间：
1999-08-03
影响因子：
11.1
通讯作者：
Peter, M
中科院分区：
文献类型：
--
作者：
Galan, JM;Peter, M
调节蛋白的泛素依赖性降解控制许多细胞过程，包括细胞周期进程、形态发生和信号转导。Skp 1 p-cullin-F-box蛋白（SCF）复合物是由核心复合物组成的泛素连接酶，核心复合物包括Skp 1 p、Cdc 53 p（被认为为复合物提供底物特异性的多种F-box蛋白之一）和泛素缀合酶Cdc 34 p，目前尚不清楚SCF复合物是如何调节的，以及生理条件如何改变它们的水平。在这里，我们表明，三个F-盒蛋白，Grr 1 p，Cdc 4p和Met 30 p，是SCF的不稳定成分，本身降解的泛素和蛋白酶体依赖的方式在体内。泛素化需要SCF的所有核心组分和完整的F-boli，这表明泛素化通过自催化机制发生在SCF复合物内，Cdc 4p和Grr 1 p本质上是不稳定的，并且它们的稳态水平在细胞周期中没有波动。总之，我们的研究结果表明，F-box蛋白的泛素依赖性降解允许在多个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和细胞周期不同阶段的进展。
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-boli, 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.