Mouse emi1 has an essential function in mitotic progression during early embryogenesis.
For successful mitotic entry and spindle assembly, mitosis-promoting factors are activated at the G(2)/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.
Lee
Ho
H
Department of Biological Sciences, Biomedical Research Center, Korea Advanced Institute of Science and Technology, 373-1 Guseoung-dong, Yuseong-gu, Daejeon 305-701, South Korea.
Lee
Dong Jun
DJ
Oh
Sang Phil
SP
Park
Hee Dong
HD
Nam
Hyun Hee
HH
Kim
Jin Man
JM
Lim
Dae-Sik
DS
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001483:Base Sequence; D002869:Chromosome Aberrations; D019925:Cyclin A / Q000378:metabolism; D004247:DNA / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005804:Genes, Lethal; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011418:Prophase / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D016196:S Phase; D008941:Spindle Apparatus / Q000473:pathology; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
D019925:Cyclin A; C498959:Emi1 protein, mouse; D011506:Proteins; D004247:DNA; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome