Human kid is degraded by the APC/CCdh1 but not by the APC/C Cdc20

Oren Feine, Amit Zur, Hiro Mahbubani, Michael Brandeis

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2516-2523
Number of pages8
JournalCell Cycle
Volume6
Issue number20
DOIs
StatePublished - 15 Oct 2007
Externally publishedYes

Bibliographical note

Funding Information:
prolines in the first place and to Alex Inberg It is easy to speculate that APC/CCdh1 specific degradation is required for the mainte‑ for the bioformatic screen. We wish to thank all nance of G1 and to set the timing for DNA replication. Yet, the role of APC/CCdh1 specific the members of the Brandeis lab in particular degradation in its very existence is still enigmatic. In addition to the APC/CCdc20 substrates Miriam Broit, Yifat Bar Zakay, Julia Sajman, that it continues to target, there is a considerable number of cell cycle proteins that seem to Jamie Simpson and Shay Rotkopf. This project be targeted exclusively by the APC/CCdh1. These include the replication regulator cdc6,10 was funded by grants from the Israel Science the mitotic kinases plk1,11 Aurora A12 and B,13,14 the cleavage furrow regulator Anillin,15 foundation (ISF 598/02), the Association of DNA methyl transferase 1,16 Sororin17 and Cdh1 itself.18 Stabilization of none of these and the Lejwa fund for Biochemistry. International Cancer Research (AICR 05‑012) proteins led to a cell cycle arrest or significant perturbation. Plk1 stabilization is the only ©2007 LANDES BIOSCIENCE11case in which such a perturbation was observed and also here this required overexpression of the protein.

Keywords

  • Aurora B
  • Cyclosome
  • Destruction box
  • KEN box
  • Kif22

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