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Open AccessArticle

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

1
Department of Pathology, University of Otago, P.O. Box 56, Dunedin 9016, New Zealand
2
Maurice Wilkins Centre for Biodiscovery, University of Otago, Dunedin 9016, New Zealand
3
Centre for Protein Research, Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin 9016, New Zealand
4
Bioinformatics Institute (A*STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, Singapore
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School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
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Department of Biological Sciences, National University of Singapore, 16 Science Drive 4, Singapore 117558, Singapore
7
Children’s Medical Research Institute, University of Sydney, NSW 2145, Australia
8
Malaghan Institute of Medical Research, Victoria University, Wellington 6242, New Zealand
*
Author to whom correspondence should be addressed.
Equal contribution.
Cancers 2020, 12(2), 315; https://doi.org/10.3390/cancers12020315
Received: 21 November 2019 / Revised: 18 January 2020 / Accepted: 25 January 2020 / Published: 29 January 2020
(This article belongs to the Special Issue Close links between Cold Shock Proteins and Cancer)
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. View Full-Text
Keywords: YB-1; cell cycle; nuclear translocation; atomistic modelling; phosphorylation YB-1; cell cycle; nuclear translocation; atomistic modelling; phosphorylation
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Mehta, S.; McKinney, C.; Algie, M.; Verma, C.S.; Kannan, S.; Harfoot, R.; Bartolec, T.K.; Bhatia, P.; Fisher, A.J.; Gould, M.L.; Parker, K.; Cesare, A.J.; Cunliffe, H.E.; Cohen, S.B.; Kleffmann, T.; Braithwaite, A.W.; Woolley, A.G. Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle. Cancers 2020, 12, 315.

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