Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/145956
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dc.contributor.authorMehta, Sunalien_US
dc.contributor.authorMcKinney, Cushlaen_US
dc.contributor.authorAlgie, Michaelen_US
dc.contributor.authorVerma, Chandra Shekharen_US
dc.contributor.authorKannan, Srinivasaraghavanen_US
dc.contributor.authorHarfoot, Rhodrien_US
dc.contributor.authorBartolec, Tara K.en_US
dc.contributor.authorBhatia, Pujaen_US
dc.contributor.authorFisher, Alistair J.en_US
dc.contributor.authorGould, Maree L.en_US
dc.contributor.authorParker, Kimen_US
dc.contributor.authorCesare, Anthony J.en_US
dc.contributor.authorCunliffe, Heather E.en_US
dc.contributor.authorCohen, Scott B.en_US
dc.contributor.authorKleffmann, Torstenen_US
dc.contributor.authorBraithwaite, Antony W.en_US
dc.contributor.authorWoolley, Adele G.en_US
dc.date.accessioned2021-01-18T06:26:36Z-
dc.date.available2021-01-18T06:26:36Z-
dc.date.issued2020-
dc.identifier.citationMehta, S., McKinney, C., Algie, M., Verma, C. S., Kannan, S., Harfoot, R., . . . Woolley, A. G. (2020). Dephosphorylation of YB-1 is required for nuclear localisation during G2 phase of the cell cycle. Cancers, 12(2), 315-. doi:10.3390/cancers12020315en_US
dc.identifier.issn2072-6694en_US
dc.identifier.urihttps://hdl.handle.net/10356/145956-
dc.description.abstractElevated levels of nuclear Y-box binding protein 1 (YB-1) are linked to poor prognosis in cancer. It has been proposed that entry into the nucleus requires specific proteasomal cleavage. However, evidence for cleavage is contradictory and high YB-1 levels are prognostic regardless of cellular location. Here, using confocal microscopy and mass spectrometry, we find no evidence of specific proteolytic cleavage. Doxorubicin treatment, and the resultant G2 arrest, leads to a significant increase in the number of cells where YB-1 is not found in the cytoplasm, suggesting that its cellular localisation is variable during the cell cycle. Live cell imaging reveals that the location of YB-1 is linked to progression through the cell cycle. Primarily perinuclear during G1 and S phases, YB-1 enters the nucleus as cells transition through late G2/M and exits at the completion of mitosis. Atomistic modelling and molecular dynamics simulations show that dephosphorylation of YB-1 at serine residues 102, 165 and 176 increases the accessibility of the nuclear localisation signal (NLS). We propose that this conformational change facilitates nuclear entry during late G2/M. Thus, the phosphorylation status of YB-1 determines its cellular location.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.language.isoenen_US
dc.relation.ispartofCancersen_US
dc.rights© 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/).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleDephosphorylation of YB-1 is required for nuclear localisation during G2 phase of the cell cycleen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationBioinformatics Institute, A*STARen_US
dc.identifier.doi10.3390/cancers12020315-
dc.description.versionPublished versionen_US
dc.identifier.pmid32013098-
dc.identifier.scopus2-s2.0-85079041867-
dc.identifier.issue2en_US
dc.identifier.volume12en_US
dc.subject.keywordsYB-1en_US
dc.subject.keywordsCell Cycleen_US
dc.description.acknowledgementWe thank the Cancer Society of New Zealand (11/07), the Maurice Wilkins Centre of New Zealand and the Dean’s Bequest Fund (Dunedin School of Medicine) for their funding support of this project. We also acknowledge the Health Research Council (HRC) of New Zealand and the Royal Society James Cook Fellowship for their ongoing support of Antony Braithwaite and his lab group. The Westmead Institute of Medical Research (WIMR) Flow Cytometry Centre, supported by the Australian NHMRC and the Cancer Institute NSW are thanked for cell sorting. Anthony Cesare and his lab are supported by grants from the NHMRC (1053195, 1106241). Srinivasaraghavan Kannan and Chandra Verma would like to thank A*STAR and National Supercomputer Centre Singapore for support. Srinivasaraghavan Kannan and Chandra Verma are founders/scientific consultants of Sinopsee Therapeutics, a biotechnology company developing molecules for therapeutic purposes; the current work does not conflict with the company.en_US
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