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PMID: 16809773 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mouse emi1 has an essential function in mitotic progression during early embryogenesis.

Molecular and cellular biology ·Vol. 26 ·No. 14 ·2006-07-00 ·Pages 5373-81

Lee H, Lee DJ, Oh SP, Park HD, Nam HH, Kim JM, Lim DS

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.

MeSH Terms
Anaphase-Promoting Complex-Cyclosome Animals Base Sequence Chromosome Aberrations Cyclin A/metabolism DNA/genetics Embryonic Development/genetics,physiology Female Genes, Lethal In Vitro Techniques Mice Mice, Inbred C57BL Mice, Knockout Mitosis/genetics,physiology Pregnancy Prophase/genetics,physiology Proteins/genetics,physiology S Phase Spindle Apparatus/pathology Ubiquitin-Protein Ligase Complexes/metabolism
Chemicals
Cyclin A Emi1 protein, mouse Proteins DNA Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lee Ho
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
Oh Sang Phil
Park Hee Dong
Nam Hyun Hee
Kim Jin Man
Lim Dae-Sik
References (39)
39 references, click to expand
  1. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation.
    Chromosoma. 1997 Nov;106(6):348-60 PMID: 9362543
  2. The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.
    Genes Dev. 1999 Feb 1;13(3):270-83 PMID: 9990852
  3. The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.
    Curr Biol. 1999 Feb 25;9(4):207-10 PMID: 10074433
  4. Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice.
    Hum Mol Genet. 1999 Jul;8(7):1145-55 PMID: 10369859
  5. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1.
    Mol Biol Cell. 2004 Dec;15(12):5623-34 PMID: 15469984
  6. Tumor susceptibility of Rassf1a knockout mice.
    Cancer Res. 2005 Jan 1;65(1):92-8 PMID: 15665283
  7. The anaphase-promoting complex: a key factor in the regulation of cell cycle.
    Oncogene. 2005 Jan 13;24(3):314-25 PMID: 15678131
  8. Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2.
    Cell. 2000 Jun 9;101(6):635-45 PMID: 10892650
  9. Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis.
    Genes Dev. 2000 Sep 15;14(18):2277-82 PMID: 10995385
  10. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype.
    Curr Biol. 2000 Nov 2;10(21):1319-28 PMID: 11084331
  11. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells.
    Nature. 2001 Jan 18;409(6818):355-9 PMID: 11201745
  12. Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.
    Cell. 2001 Jun 1;105(5):645-55 PMID: 11389834
  13. Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins.
    Genes Dev. 2001 Dec 15;15(24):3278-85 PMID: 11751633
  14. Emi1 is required for cytostatic factor arrest in vertebrate eggs.
    Nature. 2002 Apr 25;416(6883):850-4 PMID: 11976684
  15. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1).
    Nat Cell Biol. 2002 May;4(5):358-66 PMID: 11988738
  16. The anaphase-promoting complex: proteolysis in mitosis and beyond.
    Mol Cell. 2002 May;9(5):931-43 PMID: 12049731
  17. The anaphase-promoting complex: it's not just for mitosis any more.
    Genes Dev. 2002 Sep 1;16(17):2179-206 PMID: 12208841
  18. The spindle checkpoint: structural insights into dynamic signalling.
    Nat Rev Mol Cell Biol. 2002 Oct;3(10):731-41 PMID: 12360190
  19. Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E.
    Dev Cell. 2002 Sep;3(3):351-65 PMID: 12361599
  20. Differential induction and localization of mPer1 and mPer2 during advancing and delaying phase shifts.
    Eur J Neurosci. 2002 Oct;16(8):1531-40 PMID: 12405967
  21. Regulation of APC-Cdc20 by the spindle checkpoint.
    Curr Opin Cell Biol. 2002 Dec;14(6):706-14 PMID: 12473343
  22. Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo.
    Dev Cell. 2003 Jun;4(6):799-812 PMID: 12791266
  23. Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.
    Dev Cell. 2003 Jun;4(6):813-26 PMID: 12791267
  24. Emi1 proteolysis: how SCF(beta-Trcp1) helps to activate the anaphase-promoting complex.
    Mol Cell. 2003 Jun;11(6):1420-1 PMID: 12820955
  25. The spindle assembly and spindle position checkpoints.
    Annu Rev Genet. 2003;37:251-82 PMID: 14616062
  26. The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex.
    Nat Cell Biol. 2004 Feb;6(2):129-37 PMID: 14743218
  27. BUBR1 deficiency results in abnormal megakaryopoiesis.
    Blood. 2004 Feb 15;103(4):1278-85 PMID: 14576056
  28. The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer.
    Oncogene. 2004 Mar 15;23(11):2028-36 PMID: 15021890
  29. Control of APC-Cdc20 by the tumor suppressor RASSF1A.
    Cell Cycle. 2004 May;3(5):574-6 PMID: 15107619
  30. Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome.
    Proc Natl Acad Sci U S A. 2004 May 25;101(21):7937-42 PMID: 15148369
  31. The E4F protein is required for mitotic progression during embryonic cell cycles.
    Mol Cell Biol. 2004 Jul;24(14):6467-75 PMID: 15226446
  32. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
    Nature. 1989 May 25;339(6222):280-6 PMID: 2566918
  33. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53.
    Mol Cell Biol. 1996 Dec;16(12):7133-43 PMID: 8943369
  34. Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.
    Genes Dev. 1997 Jan 1;11(1):94-105 PMID: 9000053
  35. Active cyclin B1-Cdk1 first appears on centrosomes in prophase.
    Nat Cell Biol. 2003 Feb;5(2):143-8 PMID: 12524548
  36. Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity.
    Genes Dev. 2005 Feb 15;19(4):502-13 PMID: 15713843
  37. A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs.
    Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4318-23 PMID: 15753281
  38. SCF-mediated protein degradation and cell cycle control.
    Oncogene. 2005 Apr 18;24(17):2860-70 PMID: 15838520
  39. The RASSF1A isoform of RASSF1 promotes microtubule stability and suppresses tumorigenesis.
    Mol Cell Biol. 2005 Sep;25(18):8356-67 PMID: 16135822
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.00043-06
Published
2006-07-00
Pages
5373-81
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1592703
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.00043-06 PMC Full Text View journal details
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