Introduction
A common regulatory mechanism in the eukaryotic kingdom is targeted proteolysis via the 26S proteasome. Proteins destined to be degraded by this energy-dependent machine are specifically bound and poly-ubiquitinated by a cullin (aka SCF) complex, which includes ubiquitination enzymes and a substrate recognition subunit. Our work has concentrated on the substrate recognition proteins, because they are responsible for conferring specificity on the process.
There are several distinct cullin complexes in all animals and plants, each of which appears to use a distinct class of molecular adapters (see schematic). Each class of adapters can be recognized by the presence of a conserved protein domain that binds to the cognate cullin. Of specific interest for our studies are the BTB domain adapters, which function with the cullin3 complex, and the F-box domain adapters, which function with the cullin1 complex.
Both BTB adapters and F-box adapters have been studied in the context of degradation of endogenous protein substrates and are increasingly recognized as major players in this process. What particularly fascinates me about these families in nematodes (and plants) is that the vast majority of the genes are orphan adapters with no known substrate. Molecular evolution of both families suggests that most of these orphan adapters target foreign proteins, rather than endogenous proteins.
BTB domain adapters
Under development. See manuscript.
F-box domain adapters
The story with the larger F-box domain family is strikingly similar to the BTB domain adapters in every particular other than the molecular identity of the adapter protein.
Under development. See manuscript.
