Human Kid is Degraded by the APC/CCdh1 but Not by the APC/CCdc20
I don’t dare imagine what the tabloids would make from this story. For the degradologists among us, it is quite clear that the Kid in question is the chromokinesin KIF22. Interestingly, this is not the only Kid among our genes – this name is also used for the gap junction connexin GJB2 and the kidney-specific aquaporin AQP6. And while talking about ambiguity in nomenclature, the dangerous APC mentioned here is neither the antigen presenting cell (dangerous for pathogens), nor the adenomatosis polyposis coli gene (dangerous if mutated). It is the anaphase promoting complex, a multi-subunit ubiquitin ligase (dangerous mainly for proteins that hold the replicated chromsomes together).
So, what is this paper about? Kid (=Kif22) contains a so-called KEN box, a short sequence motif that is found in many proteins that are ubiquitinated and degraded during the cell cycle. The authors report that many functional KEN boxes (there are also non-functional ones) are followed by a proline residue. In this paper, they show that the presence of this proline determines that these substrates are preferentially recognized by Cdh1 (one substrate adaptor of the APC ubiquitilin ligase) but not by Cdc20 (another substrate adaptor). There are actually people who think this is interesting. Me, for one.