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dc.contributor.authorKoren, Itay
dc.contributor.authorTimms, Richard
dc.contributor.authorKula, Tomasz
dc.contributor.authorXu, Qikai
dc.contributor.authorLi, Mamie Z
dc.contributor.authorElledge, Stephen J
dc.date.accessioned2018-12-10T15:48:39Z
dc.date.available2018-12-10T15:48:39Z
dc.date.issued2018-06
dc.identifier.issn0092-8674
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286593
dc.description.abstractDegrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small and a facile technology to characterize them is lacking. Using a strategy combining Global Protein Stability (GPS) profiling with a synthetic human peptidome, we identify thousands of peptides containing degron activity. Using CRISPR screening, we established that the stability of many proteins is regulated through degrons located at their C-terminus. We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complexes adaptors that regulate C-terminal degrons including six CRL2 and two CRL4 complexes and computationally implicate multiple non-CRLs in end recognition. Human proteome analysis revealed that the C-termini of eukaryotic proteins are depleted for C-terminal degrons, suggesting an E3 ligase-dependent modulation of proteome composition. Thus, we propose that a series of ‘C-end rules’ operate to govern protein stability and shape the eukaryotic proteome.
dc.publisherElsevier
dc.titleThe Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons
dc.typeArticle
prism.endingPage1635.e14
prism.issueIdentifier7
prism.publicationDate2018
prism.publicationNameCell
prism.startingPage1622
prism.volume173
dc.identifier.doi10.17863/CAM.33906
dcterms.dateAccepted2018-04-20
rioxxterms.versionofrecord10.1016/j.cell.2018.04.028
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2018-06
dc.contributor.orcidTimms, Richard [0000-0001-7275-597X]
dc.identifier.eissn1097-4172
dc.publisher.urlhttps://www.sciencedirect.com/science/article/pii/S009286741830521X?via%3Dihub
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (201387/Z/16/Z)
cam.issuedOnline2018-05-17
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S009286741830521X?via%3Dihub
rioxxterms.freetoread.startdate2019-05-17


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