title: BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF.
abstract: Androgen receptor (AR) activity is required for prostate cancer development and progression. Thus, there is a major impetus to understand the regulation of AR action. We and others have previously shown that AR transactivation potential is dependent on the presence of an active SWI/SNF chromatin remodeling complex. However, the mechanisms underlying SWI/SNF regulation of the AR remained unsolved. We show here that the BAF57 subunit, an accessory component of the remodeling complex, is a critical regulator of AR function. We show that BAF57 is expressed in the luminal epithelia of the prostate and is required for AR-dependent transactivation in prostatic adenocarcinoma cells. Our data reveal that BAF57 can directly bind to the AR and is recruited to endogenous AR targets upon ligand activation. Loss of BAF57 or inhibition of BAF57 function severely compromised AR activity, as observed with both exogenous and endogenous AR targets. Rescue of BAF57 function restored AR activity, thus demonstrating a specific requirement of BAF57 for AR activity. This action of BAF57 proved to be dependent on SWI/SNF ATPase function. BAF57 has previously been implicated in nuclear receptor coactivator function, and we show that, although BAF57 facilitated coactivator activity, only a selected subset required BAF57 for coactivator function. Lastly, we demonstrate that both BAF57 and BRM are required for the proliferation of AR-dependent prostatic adenocarcinoma cells. In summary, these findings identify BAF57 as a critical modulator of the AR that is capable of altering AR activity, coactivator function, and AR-dependent proliferation.
authors.affiliation: Department of Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0521, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Link
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Burd
authors.forename: Erin
authors.initials: E
authors.lastname: Williams
authors.forename: Thomas
authors.initials: T
authors.lastname: Marshall
authors.forename: Gary
authors.initials: G
authors.lastname: Rosson
authors.forename: Erin
authors.initials: E
authors.lastname: Henry
authors.forename: Bernard
authors.initials: B
authors.lastname: Weissman
authors.forename: Karen E
authors.initials: KE
authors.lastname: Knudsen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000378:metabolism; D020868:Gene Silencing; D008024:Ligands; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D008024:Ligands; C110421:Mybbp1a protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; C499503:Smarca2 protein, mouse; C465207:Smarce1 protein, mouse; D014157:Transcription Factors; D000251:Adenosine Triphosphatases
references.citation: Curr Opin Cell Biol. 1998 Jun;10(3):373-83
references.pmid: 9640539
references.citation: Nature. 1998 Jul 9;394(6689):203-6
references.pmid: 9671307
references.citation: J Biol Chem. 1998 Aug 7;273(32):20213-22
references.pmid: 9685369
references.citation: Bioessays. 1998 Aug;20(8):615-26
references.pmid: 9780836
references.citation: EMBO J. 1998 Dec 1;17(23):6979-91
references.pmid: 9843504
references.citation: J Biol Chem. 1999 Mar 19;274(12):8316-21
references.pmid: 10075738
references.citation: Cell. 1999 Apr 2;97(1):53-61
references.pmid: 10199402
references.citation: J Biol Chem. 1999 Jul 2;274(27):19441-6
references.pmid: 10383460
references.citation: J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):307-13
references.pmid: 10419007
references.citation: Semin Oncol. 1999 Aug;26(4):407-21
references.pmid: 10482183
references.citation: Appl Immunohistochem Mol Morphol. 2005 Mar;13(1):66-74
references.pmid: 15722796
references.citation: Anal Biochem. 1991 Feb 1;192(2):262-7
references.pmid: 1852137
references.citation: Mol Cell Biol. 2002 May;22(10):3255-63
references.pmid: 11971959
references.citation: Mol Cell Biol. 2002 May;22(10):3373-88
references.pmid: 11971970
references.citation: Mol Biol Cell. 2002 Jun;13(6):2106-19
references.pmid: 12058073
references.citation: J Clin Oncol. 2002 Jul 1;20(13):3001-15
references.pmid: 12089231
references.citation: Nature. 2002 Jul 11;418(6894):195-9
references.pmid: 12110891
references.citation: EMBO J. 2002 Aug 1;21(15):4094-103
references.pmid: 12145209
references.citation: Oncogene. 2002 Aug 8;21(34):5193-203
references.pmid: 12149641
references.citation: Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9
references.pmid: 12231070
references.citation: J Biol Chem. 2002 Oct 25;277(43):41038-45
references.pmid: 12192000
references.citation: J Biol Chem. 2002 Nov 1;277(44):41674-85
references.pmid: 12200431
references.citation: Cancer Cell. 2002 Nov;2(5):415-25
references.pmid: 12450796
references.citation: Mol Cell. 2003 Feb;11(2):377-89
references.pmid: 12620226
references.citation: EMBO J. 2003 May 1;22(9):2146-55
references.pmid: 12727881
references.citation: Cell. 2003 Jun 27;113(7):905-17
references.pmid: 12837248
references.citation: J Biol Chem. 2003 Aug 15;278(33):30605-13
references.pmid: 12775722
references.citation: Cell. 2003 Aug 8;114(3):277-80
references.pmid: 12914692
references.citation: Mol Cell Biol. 2003 Sep;23(17):6210-20
references.pmid: 12917342
references.citation: Mol Cell Biol. 2003 Nov;23(21):7719-31
references.pmid: 14560017
references.citation: Mol Cell Biol. 2004 Feb;24(3):1188-99
references.pmid: 14729964
references.citation: J Biol Chem. 2004 Jan 30;279(5):3807-16
references.pmid: 14604992
references.citation: Biochim Biophys Acta. 2004 Mar 15;1677(1-3):30-45
references.pmid: 15020043
references.citation: Mol Cell Biol. 2004 Jul;24(13):5821-34
references.pmid: 15199138
references.citation: J Biol Chem. 2004 Aug 6;279(32):33438-46
references.pmid: 15166229
references.citation: Mol Cell Biol. 1987 Aug;7(8):2745-52
references.pmid: 3670292
references.citation: Science. 1992 Dec 4;258(5088):1598-604
references.pmid: 1360703
references.citation: EMBO J. 1993 Nov;12(11):4279-90
references.pmid: 8223438
references.citation: Mol Endocrinol. 1993 Nov;7(11):1399-407
references.pmid: 8114755
references.citation: Nucleic Acids Res. 1994 May 25;22(10):1815-20
references.pmid: 8208605
references.citation: Cell. 1994 Oct 7;79(1):119-30
references.pmid: 7923370
references.citation: Endocr Rev. 1995 Jun;16(3):271-321
references.pmid: 7671849
references.citation: Endocrinology. 1996 Mar;137(3):991-9
references.pmid: 8603613
references.citation: J Mol Endocrinol. 1999 Dec;23(3):255-75
references.pmid: 10601972
references.citation: Mol Cell Biol. 2000 Mar;20(6):1899-910
references.pmid: 10688638
references.citation: Curr Opin Genet Dev. 2000 Apr;10(2):187-92
references.pmid: 10753786
references.citation: Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59
references.pmid: 10839822
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7748-53
references.pmid: 10884406
references.citation: Mol Cell Biol. 2000 Oct;20(20):7541-9
references.pmid: 11003650
references.citation: Mol Cell Biol. 2000 Dec;20(23):8720-30
references.pmid: 11073973
references.citation: Mol Cell Biol. 2000 Dec;20(23):8879-88
references.pmid: 11073988
references.citation: Endocrinology. 2000 Dec;141(12):4698-710
references.pmid: 11108285
references.citation: J Cell Physiol. 2001 Jan;186(1):136-45
references.pmid: 11147808
references.citation: Mol Cell. 2000 Dec;6(6):1287-95
references.pmid: 11163203
references.citation: Curr Opin Genet Dev. 2001 Apr;11(2):148-54
references.pmid: 11250137
references.citation: J Biol Chem. 2001 Jan 26;276(4):2852-7
references.pmid: 11053448
references.citation: Cancer Res. 2001 Jun 1;61(11):4315-9
references.pmid: 11389051
references.citation: Oncogene. 2001 May 28;20(24):2991-3006
references.pmid: 11420714
references.citation: Urology. 2001 Aug;58(2):289-94
references.pmid: 11489729
references.citation: Semin Cancer Biol. 2001 Oct;11(5):339-52
references.pmid: 11562176
references.citation: J Biol Chem. 2002 Feb 15;277(7):4782-9
references.pmid: 11719516
references.citation: Oncogene. 2002 Feb 14;21(8):1196-207
references.pmid: 11850839
references.citation: Nat Rev Cancer. 2001 Oct;1(1):34-45
references.pmid: 11900250
references.citation: Cell. 2002 Feb 22;108(4):475-87
references.pmid: 11909519
references.citation: Mol Cell. 2002 Mar;9(3):601-10
references.pmid: 11931767
references.citation: Endocr Rev. 2002 Apr;23(2):175-200
references.pmid: 11943742
references.citation: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5517-21
references.pmid: 8643607
references.citation: EMBO J. 1996 Oct 1;15(19):5370-82
references.pmid: 8895581
references.citation: Mol Endocrinol. 1997 Feb;11(2):148-61
references.pmid: 9013762
references.citation: Gene. 1997 Mar 25;188(1):95-100
references.pmid: 9099865
references.citation: Br J Urol. 1997 Apr;79 Suppl 2:18-26
references.pmid: 9126066
references.citation: Nature. 1997 Sep 11;389(6647):194-8
references.pmid: 9296499
references.citation: Mol Cell Biol. 1997 Oct;17(10):5771-83
references.pmid: 9315635
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):492-8
references.pmid: 9435219
references.citation: Nature. 1998 May 7;393(6680):88-91
references.pmid: 9590696
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7379-84
references.pmid: 9636157