Regulation of transcription by ubiquitination without proteolysis:: Cdc34/SCFMet30-mediated inactivation of the transcription factor Met4
Regulation of transcription by ubiquitination without proteolysis:: Cdc34/SCFMet30-mediated inactivation of the transcription factor Met4
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DOI：
10.1016/s0092-8674(00)00036-2
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发表时间：
2000-08-04
期刊：
影响因子：
64.5
通讯作者：
Reed, SI
中科院分区：
文献类型：
--
作者：
Kaiser, P;Flick, K;Reed, SI
Cdc 34/SCF复合物对蛋白质的多泛素化作用靶向它们，以供26 S蛋白酶体降解。必需的F-box蛋白Met 30是泛素连接酶SCFMet 30的底物识别亚基。SCFMet 30的关键靶标是转录因子Met 4，因为MET 4的缺失抑制met 30突变体的致死性。令人惊讶的是，Met 4是一种相对稳定的蛋白质，其丰度不受Met 30的影响。然而，Met 4靶基因的转录抑制与Met 4的Cdc 34/SCFMet 30依赖性泛素化相关。在功能上，泛素化的Met 4与靶启动子相关，但不能形成功能性转录复合物。我们的数据揭示了Cdc 34/SCF的一种新的不依赖于蛋白水解的功能，并表明转录因子的泛素化可用于直接调节其活性。
Polyubiquitination of proteins by Cdc34/SCF complexes targets them for degradation by the 26S proteasome. The essential F-box protein Met30 is the substrate recognition subunit of the ubiquitin ligase SCFMet30. The critical target of SCFMet30 is the transcription factor Met4, as deletion of MET4 suppresses the lethality of met30 mutants. Surprisingly, Met4 is a relatively stable protein and its abundance is not influenced by Met30. However, transcriptional repression of Met4 target genes correlates with Cdc34 /SCFMet30-dependent ubiquitination of Met4. Functionally, ubiquitinated Met4 associates with target promoters but fails to form functional transcription complexes. Our data reveal a novel proteolysis-independent function for Cdc34/SCF and indicate that ubiquitination of transcription factors can be utilized to directly regulate their activities.