Critical role for cold shock protein YB-1 in cytokinesis

Abstract

Y-box-binding protein-1, YB-1, is essential for cell division, but it is not clear how it functions. Using live imaging and confocal microscopy we show that YB-1 functions only in the last step of division, specifically being required to initiate cytokinesis. ABSTRACTHigh levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and cancer progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cell lines resulted in cytokinesis failure, multinucleation and an increase in G1 transit time. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging of cells undergoing cytokinesis both in vitro and in zebrafish embryos, we found that YB-1 was critical for microtubule organization during cytokinesis. Using mass spectrometry we identified multiple novel phosphorylation sites on YB-1. We show that phosphorylation of YB-1 at multiple serine residues was essential for its function during cytokinesis. Using atomistic modelling we show how multiple phosphorylations alter YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining for the first time precisely how YB-1 regulates cell division.Word Count 157 / 160 words

YB-1 Knockdown Inhibits the Proliferation of Mesothelioma Cells through Multiple Mechanisms

“…YB-1 has previously been reported to bind to pericentrin and γ-tubulin during mitosis, where it regulates centrosome-based microtubule nucleation and organisation. Notably, over-expression or loss of YB-1 has been previously shown to disrupt the mitotic spindle and cause cytokinesis defects [ 61 , 62 , 63 ]. Interestingly, all three cell lines saw significant downregulation of several key S-phase and mitotic regulators such as CDC6, H2AX, PLK1, cyclin B2, Aurora B, TACC3, KIF20A and CDC20.…”