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Science 2 September 1994:
Vol. 265. no. 5177, pp. 1454 - 1458
DOI: 10.1126/science.8073290
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Articles

Science, Vol 265, Issue 5177, 1454-1458
Copyright © 1994 by American Association for the Advancement of Science

articles

Degradation of G alpha by the N-end rule pathway

K Madura and A Varshavsky

Division of Biology, California Institute of Technology, Pasadena 91125.

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.


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