Degradation signal masking by heterodimerization of MATalpha2 and MATa1 blocks their mutual destruction by the ubiquitin-proteasome pathway.
Proteolysis by the ubiquitin-proteasome pathway is often regulated, but the mechanisms underlying such regulation remain ill-defined. In Saccharomyces cerevisiae, cell type is controlled by the MAT transcription factors. The alpha2 repressor is a known ubiquitin pathway substrate in alpha haploid cells. We show that a1 is rapidly degraded in a haploids. In a/alpha diploids, alpha2 and a1 are stabilized by heterodimerization. Association depends on N-terminal coiled-coil interactions between a1 and alpha2. Residues in alpha2 important for these interactions overlap a critical determinant of an alpha2 degradation signal, which we delimit by extensive mutagenesis. Our data provide a detailed description of a natural ubiquitin-dependent degradation signal and point to a molecular mechanism for regulated turnover in which proteolytic signals are differentially masked in alternative multiprotein complexes.
Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, USA.
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Johnson
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Swanson
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Rakhilina
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Hochstrasser
D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D019281:Dimerization; D004171:Diploidy; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D006238:Haploidy; D019751:Intramolecular Transferases; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D000072235:Mating Factor; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010675:Pheromones; D046988:Proteasome Endopeptidase Complex; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins / Q000378:metabolism*
D005656:Fungal Proteins; D008074:Lipoproteins; C095063:MFA2 protein, S cerevisiae; D009097:Multienzyme Complexes; D010455:Peptides; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D000072235:Mating Factor; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D019751:Intramolecular Transferases; C068903:DEG1 protein, S cerevisiae