title: Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation.
abstract: Wnt signaling stimulates cell proliferation by promoting the G1/S transition of the cell cycle through β-catenin/TCF4-mediated gene transcription. However, Wnt signaling peaks in mitosis and contributes to the stabilization of proteins other than β-catenin, a pathway recently introduced as Wnt-dependent stabilization of proteins (Wnt/STOP). Here, we show that Wnt/STOP regulated by basal Wnt signaling during a normal cell cycle is required for proper spindle microtubule assembly and for faithful chromosome segregation during mitosis. Consequently, inhibition of basal Wnt signaling results in increased microtubule assembly rates, abnormal mitotic spindle formation and the induction of aneuploidy in human somatic cells.
authors: Section for Cellular Oncology, Institute of Molecular Oncology, Georg-August University Göttingen Göttingen Center for Molecular Biosciences (GZMB) and University Medical Center Göttingen (UMG), Göttingen, Germany.
authors: Ailine
authors: A
authors: Stolz
authors: Section for Cellular Oncology, Institute of Molecular Oncology, Georg-August University Göttingen Göttingen Center for Molecular Biosciences (GZMB) and University Medical Center Göttingen (UMG), Göttingen, Germany.
authors: Kim
authors: K
authors: Neufeld
authors: Section for Cellular Oncology, Institute of Molecular Oncology, Georg-August University Göttingen Göttingen Center for Molecular Biosciences (GZMB) and University Medical Center Göttingen (UMG), Göttingen, Germany.
authors: Norman
authors: N
authors: Ertych
authors: Section for Cellular Oncology, Institute of Molecular Oncology, Georg-August University Göttingen Göttingen Center for Molecular Biosciences (GZMB) and University Medical Center Göttingen (UMG), Göttingen, Germany holger.bastians@uni-goettingen.de.
authors: Holger
authors: H
authors: Bastians
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation; D000072261:Dishevelled Proteins; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; C501126:DKK1 protein, human; D000072261:Dishevelled Proteins; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins; C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin
keywords: Wnt signaling; aneuploidy; chromosome segregation; mitosis
references: Biochim Biophys Acta. 2008 Sep;1786(1):32-40
references: 18549824
references: Science. 1998 Sep 4;281(5382):1509-12
references: 9727977
references: J Neurosci. 2003 Apr 1;23(7):2655-64
references: 12684451
references: EMBO J. 2010 Oct 20;29(20):3470-83
references: 20823832
references: Mol Biol Cell. 2003 Jul;14(7):2844-60
references: 12857869
references: J Biol Chem. 2006 Feb 24;281(8):4787-94
references: 16365045
references: EMBO J. 2012 Jun 13;31(12):2705-13
references: 22617425
references: Science. 2007 Jun 15;316(5831):1619-22
references: 17569865
references: Curr Biol. 2010 Mar 23;20(6):R285-95
references: 20334839
references: PLoS One. 2008;3(12):e4046
references: 19107203
references: J Biol Chem. 2004 Mar 19;279(12):10829-32
references: 14744872
references: Nature. 1999 Apr 1;398(6726):422-6
references: 10201372
references: Genes Chromosomes Cancer. 2010 Mar;49(3):204-23
references: 19927377
references: Nature. 2005 Dec 8;438(7069):873-7
references: 16341017
references: IUBMB Life. 2007 Apr-May;59(4-5):316-21
references: 17505971
references: Front Mol Neurosci. 2014 May 21;7:46
references: 24904272
references: Nat Cell Biol. 2001 Apr;3(4):433-8
references: 11283620
references: Cell. 2008 Jan 11;132(1):79-88
references: 18191222
references: Mol Cell. 2014 May 22;54(4):663-74
references: 24837680
references: Bioessays. 2013 Sep;35(9):804-9
references: 23804296
references: Dev Cell. 2009 Dec;17(6):788-99
references: 20059949
references: Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10747-52
references: 16815967
references: Trends Cell Biol. 2011 Jun;21(6):374-81
references: 21306900
references: Nature. 1997 Apr 10;386(6625):623-7
references: 9121588
references: Curr Biol. 2009 Dec 1;19(22):1937-42
references: 19879145
references: Nature. 2005 Dec 8;438(7069):867-72
references: 16341016
references: Cell Div. 2012 Aug 11;7(1):19
references: 22883214
references: EMBO Rep. 2010 Apr;11(4):317-24
references: 20300119
references: Dis Model Mech. 2014 Jan;7(1):15-20
references: 24396150
references: Cell Cycle. 2006 Sep;5(18):2077-81
references: 16969101
references: Nat Cell Biol. 2014 Aug;16(8):779-91
references: 24976383
references: J Neurosci. 2004 Jun 30;24(26):6021-7
references: 15229249
references: Nat Cell Biol. 2001 Apr;3(4):429-32
references: 11283619
references: Cell. 2012 Jun 8;149(6):1192-205
references: 22682243
references: Neuron. 2014 Oct 1;84(1):63-77
references: 25242217
references: Mol Cell. 2014 Feb 6;53(3):444-57
references: 24412065
references: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5165-70
references: 19289839
references: Oncogene. 2006 Dec 4;25(57):7469-81
references: 17143291
references: Cell. 2010 Dec 23;143(7):1136-48
references: 21183076