Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint.
CDC2 Protein Kinase
/ metabolism
CRISPR-Cas Systems
Cell Cycle Checkpoints
/ drug effects
Cell Cycle Proteins
/ antagonists & inhibitors
Cyclin B1
/ genetics
Exons
Gene Editing
Genomic Instability
/ genetics
HeLa Cells
Humans
Kinetochores
/ metabolism
Mad2 Proteins
/ genetics
Mass Spectrometry
Mutation
Nuclear Envelope
/ metabolism
Nuclear Pore
/ metabolism
Nuclear Pore Complex Proteins
/ metabolism
Nuclear Proteins
/ metabolism
Protein Binding
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Proto-Oncogene Proteins
/ metabolism
Signal Transduction
/ genetics
Spindle Apparatus
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
12
07
2019
revised:
05
02
2020
accepted:
06
03
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
20
3
2021
Statut:
ppublish
Résumé
How the cell rapidly and completely reorganizes its architecture when it divides is a problem that has fascinated researchers for almost 150 yr. We now know that the core regulatory machinery is highly conserved in eukaryotes, but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major question. Cyclin B1-Cdk is the primary kinase that drives mitotic remodeling; here we show that it is targeted to the nuclear pore complex (NPC) by binding an acidic face of the kinetochore checkpoint protein, MAD1, where it coordinates NPC disassembly with kinetochore assembly. Localized cyclin B1-Cdk1 is needed for the proper release of MAD1 from the embrace of TPR at the nuclear pore so that it can be recruited to kinetochores before nuclear envelope breakdown to maintain genomic stability.
Identifiants
pubmed: 32236513
pii: 151606
doi: 10.1083/jcb.201907082
pmc: PMC7265330
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
Cyclin B1
0
MAD1L1 protein, human
0
MAD2L1 protein, human
0
Mad2 Proteins
0
Nuclear Pore Complex Proteins
0
Nuclear Proteins
0
Proto-Oncogene Proteins
0
TPR protein, human
0
Protein-Tyrosine Kinases
EC 2.7.10.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
TTK protein, human
EC 2.7.12.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
© 2020 Jackman et al.
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