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In vivo degradation of a transcriptional regulator: The yeast α2 repressor

Hochstrasser, Mark and Varshavsky, Alexander (1990) In vivo degradation of a transcriptional regulator: The yeast α2 repressor. Cell, 61 (4). pp. 697-708. ISSN 0092-8674. doi:10.1016/0092-8674(90)90481-s. https://resolver.caltech.edu/CaltechAUTHORS:20210129-142402686

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Abstract

Metabolic instability is characteristic of regulatory proteins whose in vivo concentrations must vary as a function of time. The cell type-specific α2 repressor of the yeast S. cerevisiae is shown here to have a half-life of only ∼5 min. Each of the two structural domains of α2 carries a sequence that can independently target a normally long-lived protein for rapid destruction. Moreover, these two degradation signals are shown to operate via distinct mechanisms. Mutants deficient in the degradation of α2 have been isolated and found to have a number of additional defects, indicating that the pathways responsible for α2 turnover include components with multiple functions. Finally, we demonstrate that a short-lived subunit of an oligomeric protein can be degraded in vivo without destabilizing other, long-lived subunits of the same protein. This subunit-specific degradation makes possible a novel type of posttranslational remodeling in which a heteromeric protein could be functionally modified by selective, degradation-mediated replacement of its subunits.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/0092-8674(90)90481-sDOIArticle
ORCID:
AuthorORCID
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1990 Cell Press. Received 15 December 1989, Revised 6 March 1990. We are indebted to Michael Hall (Biocenter, Basel, Switzerland) for the α2-βgal constructs. We also thank Kelly Tatchell for plasmids, William Lane (Microchemistry Laboratory, Harvard University) for protein sequencing, members of this laboratory for technical advice and for 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 (GM31530 and DK39520). M. H. is a Fellow of the Jane Coffin Childs Memorial Fund for Medical Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked ‘advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate thus fact.
Funders:
Funding AgencyGrant Number
NIHGM31530
NIHDK39520
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Issue or Number:4
DOI:10.1016/0092-8674(90)90481-s
Record Number:CaltechAUTHORS:20210129-142402686
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210129-142402686
Official Citation:Mark Hochstrasser, Alexander Varshavsky, In vivo degradation of a transcriptional regulator: The yeast α2 repressor, Cell, Volume 61, Issue 4, 1990, Pages 697-708, ISSN 0092-8674, https://doi.org/10.1016/0092-8674(90)90481-S.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107816
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:01 Feb 2021 18:14
Last Modified:16 Nov 2021 19:06

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