Substrate-mediated remodeling of methionine transport by multiple ubiquitin-dependent mechanisms in yeast cells

EMBO J. 2006 Oct 4;25(19):4436-47. doi: 10.1038/sj.emboj.7601330. Epub 2006 Sep 14.


Plasma membrane transport of single amino-acid methionine in yeast is shown to be mediated by at least seven different permeases whose activities are transcriptionaly and post-transcriptionaly regulated by different ubiquitin-dependent mechanisms. Upon high extracellular methionine exposure, three methionine-permease genes are repressed while four others are induced. SCF(Met30), SCF(Grr1) and Rsp5 ubiquitin ligases are the key actors of the ubiquitin-dependent remodeling of methionine transport. In addition to regulating the activity of Met4, the SCF(Met30) ubiquitin ligase is shown to convey an intracellular signal to a membrane initiated signaling pathway by controlling the nuclear concentration of the Stp1 transcription factor. By coupling intra- and extracellular metabolite sensing, SCF(Met30) thus allows yeast cells to accurately adjust the intermediary sulfur metabolism to the growth conditions. The multiple ubiquitin-dependent mechanisms that function in methionine transport regulation further exemplify the pervasive role of ubiquitin in the adaptation of single-cell organisms to environmental modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport
  • Enzyme Stability
  • Gene Expression Regulation, Fungal
  • Genes, Fungal / genetics
  • Methionine / metabolism*
  • Nuclear Proteins / genetics
  • Promoter Regions, Genetic / genetics
  • Proteins / metabolism
  • RNA-Binding Proteins / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity
  • Sulfur Compounds / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligase Complexes / metabolism


  • Amino Acid Transport Systems
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • MET4 protein, S cerevisiae
  • Nuclear Proteins
  • Proteins
  • RNA-Binding Proteins
  • STP1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Stp2 protein, S cerevisiae
  • Sulfur Compounds
  • Trans-Activators
  • Transcription Factors
  • Ubiquitin
  • major urinary proteins
  • Methionine
  • Ubiquitin-Protein Ligase Complexes
  • SKP Cullin F-Box Protein Ligases
  • RSP5 protein, S cerevisiae