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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2020-09-01
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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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