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).
Feine
Oren
O
The Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Zur
Amit
A
Mahbubani
Hiro
H
Brandeis
Michael
M
D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013379:Substrate Specificity; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C098764:KIF22 protein, human; D011392:Proline; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins