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Inhibition of the N-end rule pathway in living cells

Baker, Rohan T. and Varshavsky, Alexander (1991) Inhibition of the N-end rule pathway in living cells. Proceedings of the National Academy of Sciences of the United States of America, 88 (4). pp. 1090-1094. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:BAKpnas91

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Abstract

The N-end rule relates the metabolic stability of a protein to the identity of its amino-terminal residue. Previous work, using amino acid derivatives such as dipeptides to inhibit N-end rule-mediated protein degradation in an extract from mammalian reticulocytes, has demonstrated the existence of specific N-end-recognizing proteins in this in vitro system. We now show that these nontoxic amino acid derivatives, when added to growing cells of the yeast Saccharomyces cerevisiae, are able to inhibit the degradation of proteins by the N-end rule pathway in vivo. Moreover, this inhibition is shown to be selective for the two distinct classes of destabilizing amino-terminal residues in substrates of the N-end rule pathway.


Item Type:Article
Additional Information:Copyright © 1991 by the National Academy of Sciences. Communicated by Howard Green, November, 13, 1990. We thank Bonnie Bartel, Mark Hochstrasser, Phillip Ma, and Erica Johnson for their comments on the manuscript and Barbara Doran for secretarial assistance. This work was supported by grants to A.V. from the National Institutes of Health (DK39520 and AG08991). R.T.B. was supported by fellowships from the Fulbright Foundation and Life Sciences Research Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:protein degradation, ubiquitin, yeast, peptides as inhibitors, short-lived protein, degradation, residue
Record Number:CaltechAUTHORS:BAKpnas91
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:BAKpnas91
Alternative URL:http://www.pnas.org/cgi/content/abstract/88/4/1090
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:925
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 Nov 2005
Last Modified:14 Nov 2014 19:18

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