In vivo degradation of a transcriptional regulator: The yeast α2 repressor

Abstract

Metabolic instability is characteristic of regulatory proteins whose in vivo concentrations must vary as a function of time. The cell type-specific α2 repressor of the yeast S. cerevisiae is shown here to have a half-life of only ∼5 min. Each of the two structural domains of α2 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 α2 have been isolated and found to have a number of additional defects, indicating that the pathways responsible for α2 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.

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