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PMID: 32236513 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint.

The Journal of cell biology ·Vol. 219 ·No. 6 ·2020-00-01

Jackman M, Marcozzi C, Barbiero M, Pardo M, Yu L, Tyson AL, Choudhary JS, Pines J

Abstract

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.

MeSH Terms
CDC2 Protein Kinase/metabolism CRISPR-Cas Systems Cell Cycle Checkpoints/drug effects,genetics Cell Cycle Proteins/antagonists & inhibitors,genetics,metabolism Cyclin B1/genetics,metabolism Exons Gene Editing Genomic Instability/genetics HeLa Cells Humans Kinetochores/metabolism Mad2 Proteins/genetics,metabolism 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,physiology Spindle Apparatus/metabolism
Chemicals
Cell Cycle Proteins Cyclin B1 MAD1L1 protein, human MAD2L1 protein, human Mad2 Proteins Nuclear Pore Complex Proteins Nuclear Proteins Proto-Oncogene Proteins TPR protein, human Protein-Tyrosine Kinases Protein Serine-Threonine Kinases CDC2 Protein Kinase CDK1 protein, human TTK protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Jackman Mark
The Institute of Cancer Research, London, UK.
Marcozzi Chiara
The Institute of Cancer Research, London, UK.
Barbiero Martina
The Institute of Cancer Research, London, UK.
Pardo Mercedes
The Institute of Cancer Research, London, UK.
Yu Lu
The Institute of Cancer Research, London, UK.
Tyson Adam L
The Institute of Cancer Research, London, UK.
Choudhary Jyoti S
The Institute of Cancer Research, London, UK.
Pines Jonathon
The Institute of Cancer Research, London, UK.
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201907082
Published
2020-00-01
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC7265330
Subset
IM
Grants
Cancer Research UK · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.201907082 PMC Full Text View journal details
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