DEGRADATION SIGNAL MASKING BY HETERODIMERIZATION OF MAT-ALPHA-12 AND MATA1 BLOCKS THEIR MUTUAL DESTRUCTION BY THE UBIQUITIN-PROTEASOME PATHWAY

Proteolysis by the ubiquitin-proteasome pathway is often regulated, bu t the mechanisms underlying such regulation remain ill-defined. In Sac charomyces cerevisiae, cell type is controlled by the MAT transcriptio n factors. The alpha 2 repressor is a known ubiquitin pathway substrat e in cu haploid cells. We show that a1 is rapidly degraded in a haploi ds. In a/alpha diploids, alpha 2 and a1 are stabilized by heterodimeri zation. Association depends on N-terminal coiled-coil interactions bet ween al and alpha 2. Residues in alpha 2 important for these interacti ons overlap a critical determinant of an alpha 2 degradation signal, w hich we delimit by extensive mutagenesis. Our data provide a detailed description of a natural ubiquitin-dependent degradation signal and po int to a molecular mechanism for regulated turnover in which proteolyt ic signals are differentially masked in alternative multiprotein compl exes.