| First Author | Liu Y | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 5 | Pages | 1111-1122 |
| PubMed ID | 27117404 | Mgi Jnum | J:235393 |
| Mgi Id | MGI:5796230 | Doi | 10.1016/j.celrep.2016.03.083 |
| Citation | Liu Y, et al. (2016) Fbxo30 Regulates Mammopoiesis by Targeting the Bipolar Mitotic Kinesin Eg5. Cell Rep 15(5):1111-22 |
| abstractText | 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 by Kif11). 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 shRNA and/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. |
