ArticleThe EMBO journal2013
Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- Article
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- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.Nature communications · 2025Article
- Requirement of Nek2a and cyclin A2 for Wapl-dependent removal of cohesin from prophase chromatin.The EMBO journal · 2024Article
- The NEK family of serine/threonine kinases as a biomarker for cancer.Clinical and experimental medicine · 2023Review
- Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription.Nature communications · 2022Article
- Counting Degrons: Lessons From Multivalent Substrates for Targeted Protein Degradation.Frontiers in physiology · 2022Review
- Discovery and Validation of a Compound to Target Ewing's Sarcoma.Pharmaceutics · 2021Article
- Review
- A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase.EMBO reports · 2020Article
- Escape from the checkpoint: Nek2A binds a unique conformation of the APC/C-MCC complex.EMBO reports · 2020Article
- Review
- Adenoviral protein E4orf4 interacts with the polarity protein Par3 to induce nuclear rupture and tumor cell death.The Journal of cell biology · 2020Article
- Review
- Hematopoietic PBX-interacting protein is a substrate and an inhibitor of the APC/C-Cdc20 complex and regulates mitosis by stabilizing cyclin B1.The Journal of biological chemistry · 2019Article
- Induction of a Spindle-Assembly-Competent M Phase in Xenopus Egg Extracts.Current biology : CB · 2019Article
- Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase.The Journal of cell biology · 2019Article
- Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex.The EMBO journal · 2019Article
- Integration of Gene Expression Profile Data to Verify Hub Genes of Patients with Stanford A Aortic Dissection.BioMed research international · 2019Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C-Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain substrates escape this inhibition. Nek2A degradation during prometaphase depends on direct binding of Nek2A to the APC/C via a C-terminal MR dipeptide but whether this motif alone is sufficient is not clear. Here, we identify Kif18A as a novel APC/C-Cdc20 substrate and show that Kif18A degradation depends on a C-terminal LR motif. However in contrast to Nek2A, Kif18A is not degraded until anaphase showing that additional mechanisms contribute to Nek2A degradation. We find that dimerization via the leucine zipper, in combination with the MR motif, is required for stable Nek2A binding to and ubiquitination by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.