Abstract
For successful mitotic entry and spindle assembly, mitosis-promoting factors are activated at the G2/M transition stage, followed by stimulation of the anaphase-promoting complex (APC), an E3 ubiquitin ligase, to direct the ordered destruction of several critical mitotic regulators. Given that inhibition of APC activity is important for preventing premature or improper ubiquitination and destruction of substrates, several modulators and their regulation mechanisms have been studied. Emi1, an early mitotic inhibitor, is one of these regulatory factors. Here we show, by analyzing Emi1-deficient embryos, that Emi1 is essential for precise mitotic progression during early embryogenesis. Emi1−/− embryos were found to be lethal due to a defect in preimplantation development. Cell proliferation appeared to be normal, but mitotic progression was severely defective during embryonic cleavage. Moreover, multipolar spindles and misaligned chromosomes were frequently observed in Emi1 mutant cells, possibly due to premature APC activation. Our results collectively suggest that the late prophase checkpoint function of Emi1 is essential for accurate mitotic progression and embryonic viability.
Supplemental material for this article may be found at http://mcb.asm.org/.
We are grateful to Phillip Soriano and Allan Bradley for the mouse embryonic stem cells AK7 and SNL6 feeder, respectively.
This study was supported by the National Research Laboratory Program, the Korea National Cancer Center Control Program (0320370-1 and 0510582-2), and the 21st Century Frontier Functional Human Genome Project of KISTEP (Ministry of Science and Technology of Korea).