Fbxo30 is an orphan member of the F-box protein family with no known substrate or function. Here we report that, while Fbxo30−/− mice exhibit normal development, growth, lifespan, and fertility, the females fail to nurture their offspring as a result of defective mammopoiesis. Mass spectrometry analysis of Fbxo30-associated proteins revealed that Fbxo30 specifically interacts with the bipolar spindle kinesin EG5 (encoded byKif11). As a result, Fbxo30 targets Eg5 for ubiquitinylation and controls its oscillation during the cell cycle. Correlated with EG5 dysregulation, Fbxo30−/− mammary epithelial cells exhibit multiple defects in centrosome homeostasis, mitotic spindle formation, and proliferation. Effects on proliferation, centrosome homeostasis, and mammopoiesis in the Fbxo30−/− mice were rescued through normalization of Eg5 activity using shRNAand/or an EG5 inhibitor. Our data reveal the Fbxo30-Eg5 interaction as a critical checkpoint in mammopoiesis and a critical role for ubiquitinylation-regulated Eg5 oscillation in the cell cycle.
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Liu, Y., Wang, Y., Du, Z., Yan, X., Zheng, P., & Liu, Y. (2016). Fbxo30 Regulates Mammopoiesis by Targeting the Bipolar Mitotic Kinesin Eg5.. Cell Reports, 15 (5). http://dx.doi.org/10.1016/j.celrep.2016.03.083