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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/146593 |
| _version_ | 1824456061171531776 |
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| author | Mehta, Sunali Algie, Michael Al-Jabry, Tariq McKinney, Cushla Kannan, Srinivasaraghavan Verma, Chandra Shekhar Ma, Weini Zhang, Jessie Bartolec, Tara K. Masamsetti, V. Pragathi Parker, Kim Henderson, Luke Gould, Maree L. Bhatia, Puja Harfoot, Rhodri Chircop, Megan Kleffmann, Torsten Cohen, Scott B. Woolley, Adele G. Cesare, Anthony J. Braithwaite, Antony |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Mehta, Sunali Algie, Michael Al-Jabry, Tariq McKinney, Cushla Kannan, Srinivasaraghavan Verma, Chandra Shekhar Ma, Weini Zhang, Jessie Bartolec, Tara K. Masamsetti, V. Pragathi Parker, Kim Henderson, Luke Gould, Maree L. Bhatia, Puja Harfoot, Rhodri Chircop, Megan Kleffmann, Torsten Cohen, Scott B. Woolley, Adele G. Cesare, Anthony J. Braithwaite, Antony |
| author_sort | Mehta, Sunali |
| collection | NTU |
| 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. |
| first_indexed | 2025-02-19T03:48:06Z |
| format | Journal Article |
| id | ntu-10356/146593 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:48:06Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1465932023-02-28T17:09:36Z Critical role for cold shock protein YB-1 in cytokinesis Mehta, Sunali Algie, Michael Al-Jabry, Tariq McKinney, Cushla Kannan, Srinivasaraghavan Verma, Chandra Shekhar Ma, Weini Zhang, Jessie Bartolec, Tara K. Masamsetti, V. Pragathi Parker, Kim Henderson, Luke Gould, Maree L. Bhatia, Puja Harfoot, Rhodri Chircop, Megan Kleffmann, Torsten Cohen, Scott B. Woolley, Adele G. Cesare, Anthony J. Braithwaite, Antony School of Biological Sciences Bioinformatics Institute, A*STAR Science::Biological sciences YB-1 Cold Shock Protein 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. Agency for Science, Technology and Research (A*STAR) Published version This work was supported by grants from the Maurice Wilkins Centre for Molecular Biodiscovery, James Cook Fellowship (JCF-UOO1501), Cancer Society New Zealand (11/07), Health Research Council A*STAR (10-02), Health Research Council of New Zealand (15/500) and the Cancer Institute NSW (05/FRL/1-01). VPM is supported by an Australian Post-Graduate Award from the University of Sydney. SBC acknowledges the Ernest and Piroska Major Foundation for financial support. A.J.C. is supported by grants from the Australian NHMRC (1106241), the Cancer Institute NSW (11/FRL/5-02) and philanthropy from Stanford Brown, Inc. (Sydney, Australia). SK and CSV thank A*STAR (grant ID H17/01/a0/010) for support. 2021-03-02T06:14:12Z 2021-03-02T06:14:12Z 2020 Journal Article Mehta, S., Algie, M., Al-Jabri, T., McKinney, C., Kannan, S., Verma, C. S., . . . Braithwaite, A. (2020). Critical role for cold shock protein YB-1 in cytokinesis. Cancers, 12(9), 2473-. doi:10.1101/2020.03.18.997817 2072-6694 https://hdl.handle.net/10356/146593 10.3390/cancers12092473 32882852 2-s2.0-85090252687 9 12 en Cancers © 2020 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf |
| spellingShingle | Science::Biological sciences YB-1 Cold Shock Protein Mehta, Sunali Algie, Michael Al-Jabry, Tariq McKinney, Cushla Kannan, Srinivasaraghavan Verma, Chandra Shekhar Ma, Weini Zhang, Jessie Bartolec, Tara K. Masamsetti, V. Pragathi Parker, Kim Henderson, Luke Gould, Maree L. Bhatia, Puja Harfoot, Rhodri Chircop, Megan Kleffmann, Torsten Cohen, Scott B. Woolley, Adele G. Cesare, Anthony J. Braithwaite, Antony Critical role for cold shock protein YB-1 in cytokinesis |
| title | 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_short | Critical role for cold shock protein YB-1 in cytokinesis |
| title_sort | critical role for cold shock protein yb 1 in cytokinesis |
| topic | Science::Biological sciences YB-1 Cold Shock Protein |
| url | https://hdl.handle.net/10356/146593 |
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