title: Metastasis-associated protein 3 (MTA3) regulates G2/M progression in proliferating mouse granulosa cells.
abstract: Metastasis-associated protein 3 (MTA3) is a constituent of the Mi-2/nucleosome remodeling and deacetylase (NuRD) protein complex that regulates gene expression by altering chromatin structure and can facilitate cohesin loading onto DNA. The biological function of MTA3 within the NuRD complex is unknown. Herein, we show that MTA3 was expressed highly in granulosa cell nuclei of all ovarian follicle stages and at lower levels in corpora lutea. We tested the hypothesis that MTA3-NuRD complex function is required for granulosa cell proliferation. In the ovary, MTA3 interacted with NuRD proteins CHD4 and HDAC1 and the core cohesin complex protein RAD21. In cultured mouse primary granulosa cells, depletion of endogenous MTA3 using RNA interference slowed cell proliferation; this effect was rescued by coexpression of exogenous MTA3. Slowing of cell proliferation correlated with a significant decrease in cyclin B1 and cyclin B2 expression. Granulosa cell populations lacking MTA3 contained a significantly higher percentage of cells in G2/M phase and a lower percentage in S phase compared with control cells. Furthermore, MTA3 depletion slowed entry into M phase as indicated by reduced phosphorylation of histone H3 at serine 10. These findings provide the first evidence to date that MTA3 interacts with NuRD and cohesin complex proteins in the ovary in vivo and regulates G2/M progression in proliferating granulosa cells.
authors.affiliation: Reproductive Medicine Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kwintkiewicz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Padilla-Banks
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Jefferson
authors.forename: Ilana M
authors.initials: IM
authors.lastname: Jacobs
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wade
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D056744:Cyclin B1 / Q000502:physiology; D056765:Cyclin B2 / Q000502:physiology; D005260:Female; D016195:G2 Phase / Q000502:physiology*; D006107:Granulosa Cells / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009363:Neoplasm Proteins / Q000502:physiology*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D056744:Cyclin B1; D056765:Cyclin B2; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009363:Neoplasm Proteins; D000097722:Cohesins; C435499:Mta3 protein, mouse
references.citation: Mol Cell Endocrinol. 2005 Nov 24;243(1-2):12-8
references.pmid: 16219412
references.citation: Nucleic Acids Res. 1995 Jul 25;23(14):2715-23
references.pmid: 7651832
references.citation: Cell. 2004 Oct 1;119(1):75-86
references.pmid: 15454082
references.citation: Nature. 2010 Sep 23;467(7314):430-5
references.pmid: 20720539
references.citation: Exp Biol Med (Maywood). 2009 Aug;234(8):880-907
references.pmid: 19491374
references.citation: J Biol Chem. 2003 Oct 24;278(43):42560-8
references.pmid: 12920132
references.citation: Cell. 1996 Nov 29;87(5):953-9
references.pmid: 8945521
references.citation: J Biol Chem. 2010 Mar 5;285(10):6980-6
references.pmid: 20022949
references.citation: Cell. 2003 Apr 18;113(2):207-19
references.pmid: 12705869
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Biochem Biophys Res Commun. 2009 Jan 16;378(3):332-7
references.pmid: 19041848
references.citation: J Biol Chem. 2010 Mar 26;285(13):10044-10052
references.pmid: 20071335
references.citation: Mol Reprod Dev. 2010 Dec;77(12):1040-8
references.pmid: 21069797
references.citation: Curr Protoc Neurosci. 2006 Nov;Chapter 4:Unit 4.21
references.pmid: 18428637
references.citation: Mol Endocrinol. 2006 Oct;20(10):2406-17
references.pmid: 16740656
references.citation: Mol Endocrinol. 2004 Dec;18(12):2937-49
references.pmid: 15358836
references.citation: Mol Endocrinol. 2004 Apr;18(4):791-806
references.pmid: 14726488
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18475-80
references.pmid: 20937877
references.citation: Biochem Biophys Res Commun. 2003 Oct 17;310(2):267-73
references.pmid: 14521905
references.citation: Annu Rev Biochem. 2010;79:131-53
references.pmid: 20331362
references.citation: Cancer Res. 2007 Aug 1;67(15):7132-8
references.pmid: 17671180
references.citation: Semin Cell Dev Biol. 2005 Jun;16(3):335-42
references.pmid: 15840442
references.citation: Plant Mol Biol. 2000 Aug;43(5-6):677-90
references.pmid: 11089869
references.citation: Cell Cycle. 2010 Apr 1;9(7):1360-72
references.pmid: 20372054
references.citation: Biochim Biophys Acta. 2004 Mar 15;1677(1-3):52-7
references.pmid: 15020045
references.citation: Nature. 2002 Aug 29;418(6901):994-8
references.pmid: 12198550
references.citation: J Cell Biochem. 2004 Sep 1;93(1):57-67
references.pmid: 15352162
references.citation: J Cell Sci. 2007 Sep 1;120(Pt 17):2987-96
references.pmid: 17715155
references.citation: Nature. 2010 Jan 28;463(7280):474-84
references.pmid: 20110991
references.citation: J Cell Biol. 2010 Sep 6;190(5):741-9
references.pmid: 20805320
references.citation: J Cell Sci. 2003 Sep 15;116(Pt 18):3677-85
references.pmid: 12917355
references.citation: EMBO J. 2010 Sep 15;29(18):3130-9
references.pmid: 20693977
references.citation: Mol Cell. 1998 Dec;2(6):851-61
references.pmid: 9885572
references.citation: J Neurochem. 2001 May;77(4):1145-56
references.pmid: 11359880
references.citation: Mol Endocrinol. 2005 Dec;19(12):2991-3000
references.pmid: 16020485
references.citation: Biol Reprod. 1994 Feb;50(2):225-32
references.pmid: 8142540
references.citation: Endocr Rev. 1994 Dec;15(6):725-51
references.pmid: 7705279
references.citation: J Cell Biol. 2010 Sep 6;190(5):731-40
references.pmid: 20805324
references.citation: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11472-7
references.pmid: 9326634
references.citation: Chromosoma. 2009 Aug;118(4):445-57
references.pmid: 19296121
references.citation: Endocrinology. 2001 Jun;142(6):2184-93
references.pmid: 11356661
references.citation: Oncogene. 2007 Aug 13;26(37):5433-8
references.pmid: 17694084
references.citation: Nat Cell Biol. 2001 Jan;3(1):E3-6
references.pmid: 11146636
references.citation: Nature. 1996 Dec 19-26;384(6610):641-3
references.pmid: 8967953
references.citation: Nature. 1998 Oct 29;395(6705):917-21
references.pmid: 9804427