Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/145956
Title: Dephosphorylation of YB-1 is required for nuclear localisation during G2 phase of the cell cycle
Authors: Mehta, Sunali
McKinney, Cushla
Algie, Michael
Verma, Chandra Shekhar
Kannan, Srinivasaraghavan
Harfoot, Rhodri
Bartolec, Tara K.
Bhatia, Puja
Fisher, Alistair J.
Gould, Maree L.
Parker, Kim
Cesare, Anthony J.
Cunliffe, Heather E.
Cohen, Scott B.
Kleffmann, Torsten
Braithwaite, Antony W.
Woolley, Adele G.
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Mehta, 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/cancers12020315
Journal: Cancers
Abstract: Elevated 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.
URI: https://hdl.handle.net/10356/145956
ISSN: 2072-6694
DOI: 10.3390/cancers12020315
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/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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