Degron

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A degron is a specific sequence of amino acids in a protein that directs the starting place of degradation. A degron sequence can occur at either the N or C-terminal region, these are called N-Degrons or C-degrons respectively.

A temperature sensitive degron takes advantage of the N-end rule pathway, in which a destabilizing N-terminal residue dramatically decreases the in vivo half-life of a protein. The degron is a fusion protein of ubiquitin, arginine, and DHFR. DHFR is dihydrofolate reductase, a mouse-derived enzyme that functions in the synthesis of thymine. It is also heat-labile - at a higher temperature of 37°, becomes slightly unfolded and exposes an internal lysine, the site of multi-ubiquitination. Proteolysis is highly processive, and the protein is degraded by the proteosome. The degron can be fused to a gene to produce the corresponding temperature-sensitive protein. It is portable, and can be transferred on a plasmid.