Degradation Signal Masking by Heterodimerization of MATa2 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 cere-visiae, cell type is controlled by the MAT transcription factors. The a2repressor is a known ubiquitinpathway substrate in a haploid cells. We show that a1 is rapidly degraded in a haploids. In a/a diploids, a2 and a1 are stabilized by heterodimerization. Association depends on N-terminal coiled-coil interactions between a1 and a2. Residues in a2 important for these interactions overlap a critical determinant of an a2 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