Critical Role for Cold Shock Protein YB-1 in Cytokinesis.

Autor: Mehta S; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand.; Maurice Wilkins Centre for Biodiscovery, University of Otago, 9016 Dunedin, New Zealand., Algie M; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand.; Centre for Protein Research, Department of Biochemistry, University of Otago, 9054 Dunedin, New Zealand., Al-Jabry T; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., McKinney C; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand., Kannan S; Department of Biomolecular Modelling and Design, Bioinformatics Institute (A*STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, Singapore., Verma CS; Department of Biomolecular Modelling and Design, Bioinformatics Institute (A*STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, Singapore.; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.; Department of Biological Sciences, National University of Singapore, 16 Science Drive 4, Singapore 117543, Singapore., Ma W; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Zhang J; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Bartolec TK; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Masamsetti VP; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Parker K; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand., Henderson L; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand.; Maurice Wilkins Centre for Biodiscovery, University of Otago, 9016 Dunedin, New Zealand., Gould ML; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand., Bhatia P; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand., Harfoot R; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand., Chircop M; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Kleffmann T; Centre for Protein Research, Department of Biochemistry, University of Otago, 9054 Dunedin, New Zealand., Cohen SB; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Woolley AG; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand.; Maurice Wilkins Centre for Biodiscovery, University of Otago, 9016 Dunedin, New Zealand., Cesare AJ; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia., Braithwaite A; Department of Pathology, University of Otago, 9016 Dunedin, New Zealand.; Maurice Wilkins Centre for Biodiscovery, University of Otago, 9016 Dunedin, New Zealand.; Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia.; Malaghan Institute of Medical Research, 6242 Wellington, New Zealand.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 Sep 01; Vol. 12 (9). Date of Electronic Publication: 2020 Sep 01.
DOI: 10.3390/cancers12092473
Abstrakt: 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.
Databáze: MEDLINE
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