Degradation of G alpha by the N-end rule pathway.
The N-end rule relates the in vivo half-life of a protein to the identity of its amino-terminal residue. Overexpression of targeting components of the N-end rule pathway in Saccharomyces cerevisiae inhibited the growth of haploid but not diploid cells. This ploidy-dependent toxicity was shown to result from enhanced degradation of Gpa1, the alpha subunit (G alpha) of a heterotrimeric guanine nucleotide-binding protein (G protein) that regulates cell differentiation in response to mating pheromones. Sst2, a protein whose absence renders cells hypersensitive to pheromone, was essential for degradation of G alpha but not other N-end rule substrates, suggesting the involvement of an indirect, or trans-, targeting mechanism. G alpha degradation by the N-end rule pathway adds another regulatory dimension to the multitude of signaling functions mediated by G proteins.
Madura
K
K
Division of Biology, California Institute of Technology, Pasadena 91125.
Varshavsky
A
A
D002455:Cell Division; D004151:Dipeptides / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006207:Half-Life; D006238:Haploidy; D008025:Ligases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014170:Transformation, Genetic; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases
D004151:Dipeptides; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D044763:Ubiquitin-Conjugating Enzymes; C066066:UBR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D019204:GTP-Binding Proteins; D008025:Ligases