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Gid10 as an alternative N-recognin of the Pro/N-degron pathway

Melnykov, Artem and Chen, Shun-Jia and Varshavsky, Alexander (2019) Gid10 as an alternative N-recognin of the Pro/N-degron pathway. Proceedings of the National Academy of Sciences of the United States of America, 116 (32). pp. 15914-15923. ISSN 0027-8424. PMCID PMC6689949. https://resolver.caltech.edu/CaltechAUTHORS:20190725-112336927

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Abstract

In eukaryotes, N-degron pathways (formerly “N-end rule pathways”) comprise a set of proteolytic systems whose unifying feature is their ability to recognize proteins containing N-terminal degradation signals called N-degrons, thereby causing degradation of these proteins by the 26S proteasome or autophagy. Gid4, a subunit of the GID ubiquitin ligase in the yeast Saccharomyces cerevisiae, is the recognition component (N-recognin) of the GID-mediated Pro/N-degron pathway. Gid4 targets proteins by recognizing their N-terminal Pro residues or a Pro at position 2, in the presence of distinct adjoining sequence motifs. Under conditions of low or absent glucose, cells make it through gluconeogenesis. When S. cerevisiae grows on a nonfermentable carbon source, its gluconeogenic enzymes Fbp1, Icl1, Mdh2, and Pck1 are expressed and long-lived. Transition to a medium containing glucose inhibits the synthesis of these enzymes and induces their degradation by the Gid4-dependent Pro/N-degron pathway. While studying yeast Gid4, we identified a similar but uncharacterized yeast protein (YGR066C), which we named Gid10. A screen for N-terminal peptide sequences that can bind to Gid10 showed that substrate specificities of Gid10 and Gid4 overlap but are not identical. Gid10 is not expressed under usual (unstressful) growth conditions, but is induced upon starvation or osmotic stresses. Using protein binding analyses and degradation assays with substrates of GID, we show that Gid10 can function as a specific N-recognin of the Pro/N-degron pathway.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.1908304116DOIArticle
https://www.pnas.org/content/suppl/2019/07/22/1908304116.DCSupplementalPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6689949/PubMed CentralArticle
ORCID:
AuthorORCID
Melnykov, Artem0000-0002-4733-4249
Chen, Shun-Jia0000-0002-5489-4930
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 2019 National Academy of Sciences. Published under the PNAS license. Contributed by Alexander Varshavsky, June 6, 2019 (sent for review May 14, 2019; reviewed by Wolfgang Baumeister and Avram Hershko). We are grateful to the present and former members of the A.V. laboratory for their assistance and advice. This work was supported by grants to A.V. from the National Institutes of Health (GM031530 and DK039520). Author contributions: A.M., S.-J.C., and A.V. designed research; A.M. and S.-J.C. performed research; A.M., S.-J.C., and A.V. analyzed data; and A.M., S.-J.C., and A.V. wrote the paper. Reviewers: W.B., Max Planck Institute of Biochemistry; and A.H., Technion Israel Institute of Technology. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1908304116/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
NIHGM031530
NIHDK039520
Subject Keywords:Gid10; Gid4; Fbp1; ubiquitin; degradation
Issue or Number:32
PubMed Central ID:PMC6689949
Record Number:CaltechAUTHORS:20190725-112336927
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190725-112336927
Official Citation:Gid10 as an alternative N-recognin of the Pro/N-degron pathway. Artem Melnykov, Shun-Jia Chen, Alexander Varshavsky. Proceedings of the National Academy of Sciences Aug 2019, 116 (32) 15914-15923; DOI: 10.1073/pnas.1908304116
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:97405
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Jul 2019 18:42
Last Modified:03 Apr 2020 23:29

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