Degradation signal masking by heterodimerization of MATalpha2 and MATa1 blocks their mutual destruction by the ubiquitin-proteasome pathway

Cell. 1998 Jul 24;94(2):217-27. doi: 10.1016/s0092-8674(00)81421-x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cysteine Endopeptidases / metabolism*
  • Dimerization
  • Diploidy
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Haploidy
  • Intramolecular Transferases
  • Lipoproteins / chemistry
  • Lipoproteins / metabolism*
  • Mating Factor
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism*
  • Mutation
  • Peptides / chemistry
  • Peptides / metabolism*
  • Pheromones
  • Proteasome Endopeptidase Complex
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Ubiquitins / metabolism*

Substances

  • Fungal Proteins
  • Lipoproteins
  • MFA2 protein, S cerevisiae
  • Multienzyme Complexes
  • Peptides
  • Pheromones
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Mating Factor
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Intramolecular Transferases
  • DEG1 protein, S cerevisiae