Conditional Degrons for Controlling Protein Expression at the Protein Level

• Published in: Annual review of genetics Vol. 51; no. 1; pp. 83 - 102
• Main Authors: Natsume, Toyoaki, Kanemaki, Masato T
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 27.11.2017; Annual Reviews, Inc
• Subjects: Animals; conditional degron; CRISPR-Cas Systems; Deoxyribonucleic acid; Depletion; DNA; Fusion protein; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; Humans; Integrases - genetics; Integrases - metabolism; Light; Molecules; Morpholinos - genetics; Morpholinos - metabolism; mRNA; Plants - genetics; Plants - metabolism; Proteasome Endopeptidase Complex - metabolism; Protein Biosynthesis - drug effects; Protein Biosynthesis - radiation effects; Protein Domains; Protein Engineering; Protein expression; protein knockdown; Proteolysis; Proteolysis - drug effects; Proteolysis - radiation effects; Proteomics - methods; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Ribonucleic acid; RNA; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Small Molecule Libraries - pharmacology; ubiquitin-proteasome pathway; protein knockdown; ubiquitin–proteasome pathway; conditional degron; proteolysis
• ISSN: 0066-4197; 1545-2948
• DOI: 10.1146/annurev-genet-120116-024656

The conditional depletion of a protein of interest (POI) is useful not only for loss-of-function studies, but also for the modulation of biological pathways. Technologies that work at the level of DNA, mRNA, and protein are available for temporal protein depletion. Compared with technologies targeting the pretranslation steps, direct protein depletion (or protein knockdown approaches) is advantageous in terms of specificity, reversibility, and time required for depletion, which can be achieved by fusing a POI with a protein domain called a degron that induces rapid proteolysis of the fusion protein. Conditional degrons can be activated or inhibited by temperature, small molecules, light, or the expression of another protein. The conditional degron-based technologies currently available are described and discussed.