Degradation of Gα 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 (Gα) 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. Gα degradation by the N-end rule pathway adds another regulatory dimension to the multitude of signaling functions mediated by G proteins.
© 1994 American Association for the Advancement of Science. 29 April 1994; accepted 26 July 1994. We thank E. Johnson, M. Whiteway, M. Ramezani-Rad, and J. Kurjan for their gifts of plasmids and strains; J. Dohmen for his advice and reagents; and members of our laboratory, especially G. Turner, N. Johnsson, F. Lévy, C. Byrd, M. Ghislain, and J. Johnston, for comments on the manuscript. Supported by grants to A. V. from NIH.