Degradation signal masking by heterodimerization of MATα12 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 alpha 2 repressor is a known ubiquitin pathway substrate in cu haploid cells. We show that a1 is rapidly degraded in a haploids. In a/alpha diploids, alpha 2 and a1 are stabilized by heterodimerization. Association depends on N-terminal coiled-coil interactions between al and alpha 2. Residues in alpha 2 important for these interactions overlap a critical determinant of an alpha 2 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.