In vivo degradation of a transcriptional regulator: the yeast alpha 2 repressor.

M Hochstrasser, A Varshavsky

Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.

Cell 1990 May 18

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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.