In vivo degradation of a transcriptional regulator: the yeast alpha 2 repressor.
Metabolic instability is characteristic of regulatory proteins whose in vivo concentrations must vary as a function of time. The cell type-specific alpha 2 repressor of the yeast S. cerevisiae is shown here to have a half-life of only approximately 5 min. Each of the two structural domains of alpha 2 carries a sequence that can independently target a normally long-lived protein for rapid destruction. Moreover, these two degradation signals are shown to operate via distinct mechanisms. Mutants deficient in the degradation of alpha 2 have been isolated and found to have a number of additional defects, indicating that the pathways responsible for alpha 2 turnover include components with multiple functions. Finally, we demonstrate that a short-lived subunit of an oligomeric protein can be degraded in vivo without destabilizing other, long-lived subunits of the same protein. This subunit-specific degradation makes possible a novel type of posttranslational remodeling in which a heteromeric protein could be functionally modified by selective, degradation-mediated replacement of its subunits.
Hochstrasser
M
M
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Varshavsky
A
A
D000595:Amino Acid Sequence; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D006207:Half-Life; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D015202:Protein Engineering; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D005656:Fungal Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase