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Ubiquitin as a degradation signal

Johnson, Erica S. and Bartel, Bonnie and Seufert, Wolfgang and Varshavsky, Alexander (1992) Ubiquitin as a degradation signal. EMBO Journal, 11 (2). pp. 497-505. ISSN 0261-4189. PMCID PMC556480. doi:10.1002/j.1460-2075.1992.tb05080.x.

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For many short‐lived eukaryotic proteins, conjugation to ubiquitin, yielding a multiubiquitin chain, is an obligatory pre‐degradation step. The conjugated ubiquitin moieties function as a ‘secondary’ signal for degradation, in that their posttranslational coupling to a substrate protein is mediated by amino acid sequences of the substrate that act as a primary degradation signal. We report that the fusion protein ubiquitin‐‐proline‐‐beta‐galactosidase (Ub‐P‐beta gal) is short‐lived in the yeast Saccharomyces cerevisiae because its N‐terminal ubiquitin moiety functions as an autonomous, primary degradation signal. This signal mediates the formation of a multiubiquitin chain linked to Lys48 of the N‐terminal ubiquitin in Ub‐P‐beta gal. The degradation of Ub‐P‐beta gal is shown to require Ubc4, one of at least seven ubiquitin‐conjugating enzymes in S.cerevisiae. Our findings provide the first direct evidence that a monoubiquitin moiety can function as an autonomous degradation signal. This generally applicable, cis‐acting signal can be used to manipulate the in vivo half‐lives of specific intracellular proteins.

Item Type:Article
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URLURL TypeDescription CentralArticle
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1992 European Molecular Biology Organization. Received on October 22, 1991. We thank Stefan Jentsch (Friedrich-Miescher-Laboratorium, Tübingen), Jurgen Dohmen, Kiran Madura, Irene Ota and John Tobias (MIT) for helpful discussions and 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). E.S.J. and B.B. were supported by predoctoral fellowships from the National Science Foundation.
Funding AgencyGrant Number
NSF Graduate Research FellowshipUNSPECIFIED
Subject Keywords:degradation signal/protein degradation/ubiquitin/yeast
Issue or Number:2
PubMed Central ID:PMC556480
Record Number:CaltechAUTHORS:20210210-151525582
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Official Citation:Johnson, E., Bartel, B., Seufert, W. and Varshavsky, A. (1992), Ubiquitin as a degradation signal.. The EMBO Journal, 11: 497-505.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107996
Deposited By: George Porter
Deposited On:10 Feb 2021 23:50
Last Modified:16 Nov 2021 19:08

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