Rouillon A, Barbey R, Patton E E, Tyers M, Thomas D
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France.
EMBO J. 2000 Jan 17;19(2):282-94. doi: 10.1093/emboj/19.2.282.
Saccharomyces cerevisiae SCF(Met30) ubiquitin-protein ligase controls cell cycle function and sulfur amino acid metabolism. We report here that the SCF(Met30 )complex mediates the transcriptional repression of the MET gene network by triggering degradation of the transcriptional activator Met4p when intracellular S-adenosylmethionine (AdoMet) increases. This AdoMet-induced Met4p degradation is dependent upon the 26S proteasome function. Unlike Met4p, the other components of the specific transcriptional activation complexes that are assembled upstream of the MET genes do not appear to be regulated at the protein level. We provide evidence that the interaction between Met4p and the F-box protein Met30p occurs irrespective of the level of intracellular AdoMet, suggesting that the timing of Met4p degradation is not controlled by its interaction with the SCF(Met30) complex. We also demonstrate that Met30p is a short-lived protein, which localizes within the nucleus. Furthermore, transcription of the MET30 gene is regulated by intracellular AdoMet levels and is dependent upon the Met4p transcription activation function. Thus Met4p appears to control its own degradation by regulating the amount of assembled SCF(Met30) ubiquitin ligase.
酿酒酵母SCF(Met30)泛素蛋白连接酶控制细胞周期功能和硫氨基酸代谢。我们在此报告，当细胞内S-腺苷甲硫氨酸（AdoMet）增加时，SCF(Met30)复合物通过触发转录激活因子Met4p的降解来介导MET基因网络的转录抑制。这种AdoMet诱导的Met4p降解依赖于26S蛋白酶体功能。与Met4p不同，在MET基因上游组装的特异性转录激活复合物的其他组分在蛋白质水平上似乎不受调控。我们提供的证据表明，无论细胞内AdoMet水平如何，Met4p与F-box蛋白Met30p之间都会发生相互作用，这表明Met4p降解的时机不受其与SCF(Met30)复合物相互作用的控制。我们还证明Met30p是一种寿命较短的蛋白，定位于细胞核内。此外，MET30基因的转录受细胞内AdoMet水平的调控，并依赖于Met4p的转录激活功能。因此，Met4p似乎通过调节组装好的SCF(Met30)泛素连接酶的量来控制自身的降解。
