Frontiers of protein expression control with conditional degrons

Abstract

It is useful to artificially control the expression levels of a protein of interest (POI), not only for its characterization in vivo, but also for the modulation of biological pathways. Overexpression of a POI is relatively easy because it is possible to drive its expression from a transgene encoding the POI under the control of a strong promoter. However, it is more challenging to reduce or deplete the expression of a POI. A protein domain called "degron", which induces rapid proteolysis by the proteasome, can be used for this purpose. Degron-based technologies for the conditional depletion of POI--degron fusion proteins have been developed by exploiting various pathways leading to proteasomal degradation. Compared with other depletion technologies that control the expression levels of POIs at the DNA or mRNA levels, these protein-depletion approaches are advantageous in terms of specificity, reversibility, and the time required for depletion. Current conditional degron-based technologies are described and discussed.