title: Mouse emi1 has an essential function in mitotic progression during early embryogenesis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Lee
authors.forename: Sang Phil
authors.initials: SP
authors.lastname: Oh
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Park
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Nam
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Dae-Sik
authors.initials: DS
authors.lastname: Lim
mesh_terms: 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
chemical_list: D019925:Cyclin A; C498959:Emi1 protein, mouse; D011506:Proteins; D004247:DNA; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome