Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCFMet30 complex

Saccharomyces cerevisiae SCFMet30 ubiquitin-protein ligase controls cell cy cle function and sulfur amino acid metabolism. We report here that the SCFM et30 complex mediates the transcriptional repression of the MET gene networ k by triggering degradation of the transcriptional activator Met4p when int racellular S-adenosylmethionine (AdoMet) increases. This AdoMet-induced Met 4p 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 Met4 p and the F-box protein Met30p occurs irrespective of the level of intracel lular AdoMet, suggesting that the timing of Met4p degradation is not contro lled by its interaction with the SCFMet30 complex. We also demonstrate that Met30p is a short-lived protein, which localizes within the nucleus, Furth ermore, transcription of the MET30 gene is regulated by intracellular AdoMe t levels and is dependent upon the Met4p transcription activation function. Thus Met4p appears to control its own degradation by regulating the amount of assembled SCFMet30 ubiquitin ligase.