Human Kid is degraded by the APC/C(Cdh1) but not by the APC/C(Cdc20).

The APC/C(Cdh1) (anaphase promoting complex/cyclosome) targets numerous cell cycle proteins for ubiquitin mediated degradation in late mitosis and G1. The KEN box is one of two major recognition motifs of APC/C(Cdh1) substrates. This motif is however very common and shared by a tenth of the human proteome, the vast majority of which are obviously not APC/C substrates. We have observed that most known functional KEN boxes are followed by a proline residue and show that this proline plays a role in APC/C(Cdh1) specific degradation. This insight can be instrumental for identifying novel APC/C(Cdh1) substrates. We used this KENxP motif to identify human Aurora B and Kid as APC/C(Cdh1) substrates. The degradation of Xenopus XKid at metaphase by APC/C(Cdc20) is essential for chromatid segregation. Human Kid in contrast is degraded later and its APC/C(Cdh1) specific degradation is not required for mitotic progress. It is thus likely that Kid inactivation in G1 takes place both by nuclear sequestration and degradation by the APC/C(Cdh1).