ArticleGenes & development2007
Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint.
Article in Genes & development, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 189 citations in OpenAlex.
- BubR1 TPR domain supports the mitotic checkpoint by promoting MCC formation and MCC-APC/C interaction.Communications biology · 2026Article
- A comparative study of the cryo-EM structures ofeLife · 2024Article
- MAPK-dependent control of mitotic progression in S. pombe.BMC biology · 2024Article
- Role of spindle assembly checkpoint proteins in gametogenesis and embryogenesis.Frontiers in cell and developmental biology · 2024Review
- Targeting TRIP13 for overcoming anticancer drug resistance (Review).Oncology reports · 2023Article
- Principles and dynamics of spindle assembly checkpoint signalling.Nature reviews. Molecular cell biology · 2023Review
- Spindle assembly checkpoint activation and silencing at kinetochores.Seminars in cell & developmental biology · 2021Review
- Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation.Frontiers in cell and developmental biology · 2021Review
- Paradoxical mitotic exit induced by a small molecule inhibitor of APC/CNature chemical biology · 2020Article
- The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity.The Journal of biological chemistry · 2020Article
- 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
- Posing the APC/C E3 Ubiquitin Ligase to Orchestrate Cell Division.Trends in cell biology · 2019Review
- Implications of alternative routes to APC/C inhibition by the mitotic checkpoint complex.PLoS computational biology · 2018Article
- Perturbing mitosis for anti-cancer therapy: is cell death the only answer?EMBO reports · 2018Review
- BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling.Current biology : CB · 2017Article
- Playing polo during mitosis: PLK1 takes the lead.Oncogene · 2017Review
- Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae.Cellular signalling · 2017Article
- Taming the Beast: Control of APC/CCold Spring Harbor symposia on quantitative biology · 2017Article
- The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C.Molecular cell · 2016Article
- Phylogenomics-guided discovery of a novel conserved cassette of short linear motifs in BubR1 essential for the spindle checkpoint.Open biology · 2016Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Inappropriate attachment/tension between chromosomal kinetochores and the kinetochore microtubules activates the spindle assembly checkpoint, which delays anaphase by blocking the ubiquitin-mediated degradation of securin/Pds1p by APCCdc20. The checkpoint proteins Mad2 and Mad3/BubR1 bind to Cdc20, although how they inhibit APCCdc20 is unclear. We investigated the roles of two evolutionarily conserved KEN boxes and a D box within Mad3/BubR1. Although such motifs usually mediate APC-substrate recognition and ubiquitination, they have no apparent role in Mad3p turnover in Saccharomyces cerevisiae. Instead, these motifs are important for Mad3p function in the checkpoint and for binding to Cdc20p. We show that the Mad3p D box and KEN boxes function together to mediate Cdc20p-Mad3p interaction and that Mad3p and an anaphase-promoting complex (APC) substrate, Hsl1p, compete for Cdc20p binding in a D-box- and KEN-box-dependent manner. In vivo, we observed an increased binding of Cdc20p to Mad3p and decreased binding to Hsl1p upon checkpoint activation. Furthermore, we demonstrate that Mad2p stimulates the association between Mad3p and Cdc20p and that this stimulated binding requires KEN box 1 within Mad3p. These findings implicate Mad3p as a pseudosubstrate inhibitor of APCCdc20, competing with APC substrates for Cdc20p binding. We present a model aimed at unifying previous analyses of checkpoint function by focusing on the Mad3-Cdc20 interaction.
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Registered trials
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.