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S1P signaling accelerates mitosis

Here, we found that SphK1 and its product S1P regulate mitosis. SphK1 promoted proper mitotic progression in a SAC-dependent manner, whereas increased SphK1 activity accelerated mitosis (Movie S1 and Movie S2). S1P overrode the mitotic spindle checkpoint, led to premature mitotic exit, and induced chromosome segregation defects through a pathway involving S1P5 and phosphatidylinositol 3-kinase (PI3K)–AKT signaling that was at least partially mediated by Polo-like kinase 1 (PLK1).

In summary, our study uncovers a previously unknown role for SphK1-S1P-S1P5 signaling in controlling proper mitotic progression through prometaphase to the metaphase-to-anaphase transition. More generally, our findings support the concept that cellular micro- environment plays an important role in coordination of mitosis and paves the way for future studies evaluating the relationship between extracellular signals, mitotic progression, and chromosomal stability.

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Movie S1. Representative movie showing mitosis in a GFP-expressing cell.


Movie S2. Representative movie showing mitosis in a GFP-SphK1–expressing cell.