Dual regulation of the met4 transcription factor by ubiquitin-dependent degradation and inhibition of promoter recruitment

Mol Cell. 2002 Jul;10(1):69-80. doi: 10.1016/s1097-2765(02)00561-0.


The ubiquitin system has been recently implicated in various aspects of transcriptional regulation, including proteasome-dependent degradation of transcriptional activators. In yeast, the activator Met4 is inhibited by the SCF(Met30) ubiquitin ligase, which recognizes and oligo-ubiquitylates Met4. Here, we demonstrate that in minimal media, Met4 is ubiquitylated and rapidly degraded in response to methionine excess, whereas in rich media, Met4 is oligo-ubiquitylated but remains stable. In the latter growth condition, oligo-ubiquitylated Met4 is not recruited to MET gene promoters, but is recruited to the SAM genes, which are required for production of S-adenosylmethionine, an unstable metabolite that is not present in rich medium. Thus, ubiquitylation not only regulates Met4 by distinct degradation-dependent and -independent mechanisms, but also controls differential recruitment of a single transcription factor to distinct promoters, thereby diversifying transcriptional activator specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors
  • Blotting, Western
  • Cell Division
  • Culture Media
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal*
  • Genes, Fungal / genetics
  • Methionine / pharmacology
  • Peptide Synthases / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • SKP Cullin F-Box Protein Ligases
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor TFIIB
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Ubiquitin / metabolism*


  • Basic-Leucine Zipper Transcription Factors
  • Culture Media
  • DNA-Binding Proteins
  • MET4 protein, S cerevisiae
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factor TFIIB
  • Transcription Factors
  • Ubiquitin
  • Methionine
  • SKP Cullin F-Box Protein Ligases
  • Peptide Synthases