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Human Kid is Degraded by the APC/CCdh1 but Not by the APC/CCdc20

Oren Feine, Amit Zur, Hiro Mahbubani and Michael Brandeis

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The APC/CCdh1 (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/CCdh1 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/CCdh1 specific degradation. This insight can be instrumental for identifying novel APC/CCdh1 substrates. We used this KENxP motif to identify human Aurora B and Kid as APC/CCdh1 substrates. The degradation of Xenopus XKid at metaphase by APC/CCdc20 is essential for chromatid segregation. Human Kid in contrast is degraded later and its APC/CCdh1 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/CCdh1.

Authors

Oren Feine

The Hebrew University of Jerusalem; Jerusalem, Israel

Amit Zur

The Hebrew University of Jerusalem; Jerusalem, Israel

Hiro Mahbubani

Cancer Research UK; South Mimms UK

Michael Brandeis

The Hebrew University of Jerusalem; Jerusalem, Israel

Purchase article for $19

Subscribe to this journal for $129/year