Critical Role for Cold Shock Protein YB-1 in Cytokinesis

High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immor...

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Main Authors: Sunali Mehta, Michael Algie, Tariq Al-Jabry, Cushla McKinney, Srinivasaraghavan Kannan, Chandra S Verma, Weini Ma, Jessie Zhang, Tara K. Bartolec, V. Pragathi Masamsetti, Kim Parker, Luke Henderson, Maree L Gould, Puja Bhatia, Rhodri Harfoot, Megan Chircop, Torsten Kleffmann, Scott B Cohen, Adele G Woolley, Anthony J Cesare, Antony Braithwaite
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/9/2473
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spelling doaj-39b16761981742bf9426cc54ff1ffc532020-11-25T03:19:26ZengMDPI AGCancers2072-66942020-09-01122473247310.3390/cancers12092473Critical Role for Cold Shock Protein YB-1 in CytokinesisSunali Mehta0Michael Algie1Tariq Al-Jabry2Cushla McKinney3Srinivasaraghavan Kannan4Chandra S Verma5Weini Ma6Jessie Zhang7Tara K. Bartolec8V. Pragathi Masamsetti9Kim Parker10Luke Henderson11Maree L Gould12Puja Bhatia13Rhodri Harfoot14Megan Chircop15Torsten Kleffmann16Scott B Cohen17Adele G Woolley18Anthony J Cesare19Antony Braithwaite20Department of Pathology, University of Otago, 9016 Dunedin, New ZealandDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandDepartment of Biomolecular Modelling and DesignBioinformatics Institute (A*STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, SingaporeDepartment of Biomolecular Modelling and DesignBioinformatics Institute (A*STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, SingaporeChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaCentre for Protein Research, Department of Biochemistry, University of Otago, 9054 Dunedin, New ZealandChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandChildren’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaDepartment of Pathology, University of Otago, 9016 Dunedin, New ZealandHigh levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division.https://www.mdpi.com/2072-6694/12/9/2473YB-1cold shock proteincytokinesispost-translational modificationphosphorylationlive-cell imaging
collection DOAJ
language English
format Article
sources DOAJ
author Sunali Mehta
Michael Algie
Tariq Al-Jabry
Cushla McKinney
Srinivasaraghavan Kannan
Chandra S Verma
Weini Ma
Jessie Zhang
Tara K. Bartolec
V. Pragathi Masamsetti
Kim Parker
Luke Henderson
Maree L Gould
Puja Bhatia
Rhodri Harfoot
Megan Chircop
Torsten Kleffmann
Scott B Cohen
Adele G Woolley
Anthony J Cesare
Antony Braithwaite
spellingShingle Sunali Mehta
Michael Algie
Tariq Al-Jabry
Cushla McKinney
Srinivasaraghavan Kannan
Chandra S Verma
Weini Ma
Jessie Zhang
Tara K. Bartolec
V. Pragathi Masamsetti
Kim Parker
Luke Henderson
Maree L Gould
Puja Bhatia
Rhodri Harfoot
Megan Chircop
Torsten Kleffmann
Scott B Cohen
Adele G Woolley
Anthony J Cesare
Antony Braithwaite
Critical Role for Cold Shock Protein YB-1 in Cytokinesis
Cancers
YB-1
cold shock protein
cytokinesis
post-translational modification
phosphorylation
live-cell imaging
author_facet Sunali Mehta
Michael Algie
Tariq Al-Jabry
Cushla McKinney
Srinivasaraghavan Kannan
Chandra S Verma
Weini Ma
Jessie Zhang
Tara K. Bartolec
V. Pragathi Masamsetti
Kim Parker
Luke Henderson
Maree L Gould
Puja Bhatia
Rhodri Harfoot
Megan Chircop
Torsten Kleffmann
Scott B Cohen
Adele G Woolley
Anthony J Cesare
Antony Braithwaite
author_sort Sunali Mehta
title Critical Role for Cold Shock Protein YB-1 in Cytokinesis
title_short Critical Role for Cold Shock Protein YB-1 in Cytokinesis
title_full Critical Role for Cold Shock Protein YB-1 in Cytokinesis
title_fullStr Critical Role for Cold Shock Protein YB-1 in Cytokinesis
title_full_unstemmed Critical Role for Cold Shock Protein YB-1 in Cytokinesis
title_sort critical role for cold shock protein yb-1 in cytokinesis
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2020-09-01
description High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division.
topic YB-1
cold shock protein
cytokinesis
post-translational modification
phosphorylation
live-cell imaging
url https://www.mdpi.com/2072-6694/12/9/2473
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