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...

Full description

Bibliographic Details
Main Authors: Yibo Luo, Ejaz Ahmad, Song-Tao Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-05-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fcell.2018.00051/full
_version_ 1819071407859957760
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.
first_indexed 2024-12-21T17:21:21Z
format Article
id doaj.art-4599522ca7fc4ab080e363aa1c192fb8
institution Directory Open Access Journal
issn 2296-634X
language English
last_indexed 2024-12-21T17:21:21Z
publishDate 2018-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cell and Developmental Biology
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
work_keys_str_mv AT yiboluo mad1kinetochorereceptorsandcatalyticmechanisms
AT ejazahmad mad1kinetochorereceptorsandcatalyticmechanisms
AT songtaoliu mad1kinetochorereceptorsandcatalyticmechanisms