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Degradation of Gα by the N-End Rule Pathway

Madura, Kiran and Varshavsky, Alexander (1994) Degradation of Gα by the N-End Rule Pathway. Science, 265 (5177). pp. 1454-1458. ISSN 0036-8075.

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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.

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Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 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.
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Issue or Number:5177
Record Number:CaltechAUTHORS:20150121-092636074
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Official Citation:Madura, K., & Varshavsky, A. (1994). Degradation of G alpha by the N-end rule pathway. Science, 265(5177), 1454-1458. doi: 10.1126/science.8073290
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53926
Deposited By: Jason Perez
Deposited On:22 Jan 2015 00:05
Last Modified:25 Nov 2020 22:53

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