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

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Authors

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

Document Type

Journal Article

Date

2020-06-01

Date Accepted

2020-03-06

Date Available

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.

Citation

The Journal of cell biology, 2020, 219 (6)

Source Title

Publisher

ROCKEFELLER UNIV PRESS

ISSN

0021-9525

eISSN

1540-8140

Collections

Research Team

Functional Proteomics Group

Notes