EMC3 regulates mesenchymal cell survival via control of the mitotic spindle assembly

Eukaryotic cells transit through the cell cycle to produce two daughter cells. Dys-regulation of the cell cycle leads to cell death or tumorigenesis. Herein, we found a subunit of the ER membrane complex, EMC3, as a key regulator of cell cycle. Conditional deletion of Emc3 in mouse embryonic mesoderm led to reduced size and patterning defects of multiple organs. Emc3 deficiency impaired cell pro-liferation, causing spindle assembly defects, chromosome mis-segregation, cell cycle arrest at G2/M, and apoptosis. Upon entry into mitosis, mesenchymal cells upregulate EMC3 protein levels and localize EMC3 to the mitotic centrosomes. Further analysis indicated that EMC3 works together with VCP to tightly regulate the levels and activity of Aurora A, an essential factor for centrosome function and mitotic spindle assembly: while overexpression of EMC3 or VCP degraded Aurora A, their loss led to increased Aurora A stability but reduced Aurora A phosphorylation in mitosis.

Automated summary

Eukaryotic cells go through the cell cycle to produce two daughter cells. Dys-regulation of the cell cycle can result in cell death or tumorigenesis. This study shows that EMC3, a subunit of the ER membrane complex, is a key regulator of the cell cycle. Its deficiency leads to defects in organ size and patterning, impaired cell proliferation, spindle assembly defects, chromosome mis-segregation, cell cycle arrest, and apoptosis. EMC3 works together with VCP to regulate the levels and activity of Aurora A, an essential factor for centrosome function and mitotic spindle assembly.