Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.

Cyclin-dependent kinase 1 (Cdk1) complexed with cyclin B phosphorylates multiple sites on hundreds of proteins during mitosis. However, it is not fully understood how multi-site mitotic phosphorylation by cyclin B-Cdk1 controls the structures and functions of individual substrates. Here we develop a...

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Main Authors: Keishi Shintomi, Yuki Masahara-Negishi, Masami Shima, Shoji Tane, Tatsuya Hirano
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0299003
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author Keishi Shintomi
Yuki Masahara-Negishi
Masami Shima
Shoji Tane
Tatsuya Hirano
author_facet Keishi Shintomi
Yuki Masahara-Negishi
Masami Shima
Shoji Tane
Tatsuya Hirano
author_sort Keishi Shintomi
collection DOAJ
description Cyclin-dependent kinase 1 (Cdk1) complexed with cyclin B phosphorylates multiple sites on hundreds of proteins during mitosis. However, it is not fully understood how multi-site mitotic phosphorylation by cyclin B-Cdk1 controls the structures and functions of individual substrates. Here we develop an easy-to-use protocol to express recombinant vertebrate cyclin B and Cdk1 in insect cells from a single baculovirus vector and to purify their complexes with excellent homogeneity. A series of in-vitro assays demonstrate that the recombinant cyclin B-Cdk1 can efficiently and specifically phosphorylate the SP and TP motifs in substrates. The addition of Suc1 (a Cks1 homolog in fission yeast) accelerates multi-site phosphorylation of an artificial substrate containing TP motifs. Importantly, we show that mitosis-specific multi-subunit and multi-site phosphorylation of the condensin I complex can be recapitulated in vitro using recombinant cyclin B-Cdk1-Suc1. The materials and protocols described here will pave the way for dissecting the biochemical basis of critical mitotic processes that accompany Cdk1-mediated large-scale phosphorylation.
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spelling doaj-art-3a2f855061af4b0e88a07d544c2fa9782025-08-20T03:37:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01193e029900310.1371/journal.pone.0299003Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.Keishi ShintomiYuki Masahara-NegishiMasami ShimaShoji TaneTatsuya HiranoCyclin-dependent kinase 1 (Cdk1) complexed with cyclin B phosphorylates multiple sites on hundreds of proteins during mitosis. However, it is not fully understood how multi-site mitotic phosphorylation by cyclin B-Cdk1 controls the structures and functions of individual substrates. Here we develop an easy-to-use protocol to express recombinant vertebrate cyclin B and Cdk1 in insect cells from a single baculovirus vector and to purify their complexes with excellent homogeneity. A series of in-vitro assays demonstrate that the recombinant cyclin B-Cdk1 can efficiently and specifically phosphorylate the SP and TP motifs in substrates. The addition of Suc1 (a Cks1 homolog in fission yeast) accelerates multi-site phosphorylation of an artificial substrate containing TP motifs. Importantly, we show that mitosis-specific multi-subunit and multi-site phosphorylation of the condensin I complex can be recapitulated in vitro using recombinant cyclin B-Cdk1-Suc1. The materials and protocols described here will pave the way for dissecting the biochemical basis of critical mitotic processes that accompany Cdk1-mediated large-scale phosphorylation.https://doi.org/10.1371/journal.pone.0299003
spellingShingle Keishi Shintomi
Yuki Masahara-Negishi
Masami Shima
Shoji Tane
Tatsuya Hirano
Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.
PLoS ONE
title Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.
title_full Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.
title_fullStr Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.
title_full_unstemmed Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.
title_short Recombinant cyclin B-Cdk1-Suc1 capable of multi-site mitotic phosphorylation in vitro.
title_sort recombinant cyclin b cdk1 suc1 capable of multi site mitotic phosphorylation in vitro
url https://doi.org/10.1371/journal.pone.0299003
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