Mapping the Landscape of a Eukaryotic Degronome

Yifat Geffen, Alon Appleboim, Richard G. Gardner, Nir Friedman*, Ronen Sadeh, Tommer Ravid

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The ubiquitin-proteasome system (UPS) for protein degradation has been under intensive study, and yet, we have only partial understanding of mechanisms by which proteins are selected to be targeted for proteolysis. One of the obstacles in studying these recognition pathways is the limited repertoire of known degradation signals (degrons). To better understand what determines the susceptibility of intracellular proteins to degradation by the UPS, we developed an unbiased method for large-scale identification of eukaryotic degrons. Using a reporter-based high-throughput competition assay, followed by deep sequencing, we measured a degradation potency index for thousands of native polypeptides in a single experiment. We further used this method to identify protein quality control (PQC)-specific and compartment-specific degrons. Our method provides an unprecedented insight into the yeast degronome, and it can readily be modified to study protein degradation signals and pathways in other organisms and in various settings.

Original languageAmerican English
Pages (from-to)1055-1065
Number of pages11
JournalMolecular Cell
Volume63
Issue number6
DOIs
StatePublished - 15 Sep 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

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