MAD1: Kinetochore Receptors and Catalytic Mechanisms
The mitotic checkpoint monitors kinetochore-microtubule attachment, delays anaphase onset and prevents aneuploidy when unattached or tensionless kinetochores are present in cells. Mitotic arrest deficiency 1 (MAD1) is one of the evolutionarily conserved core mitotic checkpoint proteins. MAD1 forms a...
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Format: | Article |
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Frontiers Media S.A.
2018-05-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fcell.2018.00051/full |
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author | Yibo Luo Ejaz Ahmad Song-Tao Liu |
author_facet | Yibo Luo Ejaz Ahmad Song-Tao Liu |
author_sort | Yibo Luo |
collection | DOAJ |
description | The mitotic checkpoint monitors kinetochore-microtubule attachment, delays anaphase onset and prevents aneuploidy when unattached or tensionless kinetochores are present in cells. Mitotic arrest deficiency 1 (MAD1) is one of the evolutionarily conserved core mitotic checkpoint proteins. MAD1 forms a cell cycle independent complex with MAD2 through its MAD2 interaction motif (MIM) in the middle region. Such a complex is enriched at unattached kinetochores and functions as an unusual catalyst to promote conformational change of additional MAD2 molecules, constituting a crucial signal amplifying mechanism for the mitotic checkpoint. Only MAD2 in its active conformation can be assembled with BUBR1 and CDC20 to form the Mitotic Checkpoint Complex (MCC), which is a potent inhibitor of anaphase onset. Recent research has shed light on how MAD1 is recruited to unattached kinetochores, and how it carries out its catalytic activity. Here we review these advances and discuss their implications for future research. |
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format | Article |
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issn | 2296-634X |
language | English |
last_indexed | 2024-12-21T17:21:21Z |
publishDate | 2018-05-01 |
publisher | Frontiers Media S.A. |
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spelling | doaj.art-4599522ca7fc4ab080e363aa1c192fb82022-12-21T18:56:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2018-05-01610.3389/fcell.2018.00051371712MAD1: Kinetochore Receptors and Catalytic MechanismsYibo LuoEjaz AhmadSong-Tao LiuThe mitotic checkpoint monitors kinetochore-microtubule attachment, delays anaphase onset and prevents aneuploidy when unattached or tensionless kinetochores are present in cells. Mitotic arrest deficiency 1 (MAD1) is one of the evolutionarily conserved core mitotic checkpoint proteins. MAD1 forms a cell cycle independent complex with MAD2 through its MAD2 interaction motif (MIM) in the middle region. Such a complex is enriched at unattached kinetochores and functions as an unusual catalyst to promote conformational change of additional MAD2 molecules, constituting a crucial signal amplifying mechanism for the mitotic checkpoint. Only MAD2 in its active conformation can be assembled with BUBR1 and CDC20 to form the Mitotic Checkpoint Complex (MCC), which is a potent inhibitor of anaphase onset. Recent research has shed light on how MAD1 is recruited to unattached kinetochores, and how it carries out its catalytic activity. Here we review these advances and discuss their implications for future research.http://journal.frontiersin.org/article/10.3389/fcell.2018.00051/fullmitosismitotic checkpointkinetochoreMAD1MAD2protein conformation |
spellingShingle | Yibo Luo Ejaz Ahmad Song-Tao Liu MAD1: Kinetochore Receptors and Catalytic Mechanisms Frontiers in Cell and Developmental Biology mitosis mitotic checkpoint kinetochore MAD1 MAD2 protein conformation |
title | MAD1: Kinetochore Receptors and Catalytic Mechanisms |
title_full | MAD1: Kinetochore Receptors and Catalytic Mechanisms |
title_fullStr | MAD1: Kinetochore Receptors and Catalytic Mechanisms |
title_full_unstemmed | MAD1: Kinetochore Receptors and Catalytic Mechanisms |
title_short | MAD1: Kinetochore Receptors and Catalytic Mechanisms |
title_sort | mad1 kinetochore receptors and catalytic mechanisms |
topic | mitosis mitotic checkpoint kinetochore MAD1 MAD2 protein conformation |
url | http://journal.frontiersin.org/article/10.3389/fcell.2018.00051/full |
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