关键词： C terminus CRL Cullin DesCEND E3 ubiquitin ligase GPS degron global protein stability protein degradation ubiquitination

Mesh ： Amino Acid Motifs Animals Antigens, Neoplasm / metabolism CRISPR-Cas Systems / genetics Computational Biology / methods Genetic Vectors / genetics metabolism HEK293 Cells Humans Lentivirus / genetics Leupeptins / pharmacology Open Reading Frames / genetics Peptides / metabolism Proteasome Endopeptidase Complex / chemistry metabolism Protein Stability / drug effects Protein Subunits / metabolism Proteolysis Proteome / genetics metabolism Receptors, Cytokine / genetics metabolism Ubiquitin-Protein Ligases / metabolism

来  源：   DOI：10.1016/j.cell.2018.04.028   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Degrons 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. Employing CRISPR screening, we establish that the stability of many proteins is regulated through degrons located at their C terminus. We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complex adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition. 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.
摘要：
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