title: Transcriptional synergy between melanoma antigen gene protein-A11 (MAGE-11) and p300 in androgen receptor signaling.
abstract: Androgen receptor (AR)-mediated gene regulation involves interactions with coregulatory proteins that include the melanoma antigen gene protein-A11 (MAGE-11). To understand the functional significance of sequence similarity between MAGE-11 and the adenovirus early protein E1A, we determined whether MAGE-11 contributes to AR transcriptional activity through an interaction with p300, a potent and ubiquitous transcriptional regulator. Here, we report that MAGE-11 interacts with the NH(2)-terminal region of p300 through the MAGE-11 MXXIF motif (185)MXXIF(189), with transcriptional activity depending on the MAGE-11 F-box and MAPK phosphorylation. The MAGE-11- and p300-dependent increase in AR transactivation required the NH(2)-terminal regions of AR and p300, p300 acetyltransferase activity, and the AR FXXLF motif (23)FQNLF(27) interaction with MAGE-11. MAGE-11 linked AR to p300 and the p160 coactivator, transcriptional intermediary protein 2 (TIF2). The p300 NH(2)-terminal FXXLF motif (33)FGSLF(37) was required for transcriptional activation by TIF2. Increased expression of p300 decreased the ubiquitinylation of MAGE-11 and transiently increased endogenous MAGE-11 levels. Autoacetylation of p300 and decreased acetylation of TIF2 were evident in the MAGE-11, p300, and TIF2 complex. The studies suggest that MAGE-11 links NH(2)-terminal domains of AR and p300 to promote transcriptional synergy through a cadre of FXXLF-related interacting motifs.
authors.affiliation: Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Askew
authors.forename: Suxia
authors.initials: S
authors.lastname: Bai
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Blackwelder
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wilson
mesh_terms: D020816:Amino Acid Motifs; D000728:Androgens / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D000728:Androgens; D000951:Antigens, Neoplasm; C110882:MAGEA11 protein, human; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
references.citation: Nature. 1995 Mar 2;374(6517):85-8
references.pmid: 7870179
references.citation: Oncogene. 1996 Apr 4;12(7):1565-9
references.pmid: 8622873
references.citation: Nature. 1995 Mar 2;374(6517):81-4
references.pmid: 7870178
references.citation: Mol Cancer Res. 2009 Apr;7(4):523-35
references.pmid: 19372581
references.citation: J Biol Chem. 2007 Aug 31;282(35):25801-16
references.pmid: 17591767
references.citation: J Biol Chem. 2003 Jun 27;278(26):23691-8
references.pmid: 12714604
references.citation: Genes Dev. 1994 Apr 15;8(8):869-84
references.pmid: 7523245
references.citation: J Biol Chem. 2004 Nov 19;279(47):49395-405
references.pmid: 15337767
references.citation: Nature. 1996 Sep 5;383(6595):99-103
references.pmid: 8779723
references.citation: J Biol Chem. 1991 Jan 5;266(1):510-8
references.pmid: 1985913
references.citation: Mol Cell Biol. 2005 Feb;25(4):1238-57
references.pmid: 15684378
references.citation: J Biol Chem. 2001 Nov 9;276(45):42293-301
references.pmid: 11551963
references.citation: Mol Cell Biol. 1998 Mar;18(3):1369-78
references.pmid: 9488452
references.citation: Mol Endocrinol. 1988 Dec;2(12):1265-75
references.pmid: 3216866
references.citation: Cancer Res. 2002 Oct 15;62(20):5632-6
references.pmid: 12384515
references.citation: Nature. 1998 Nov 12;396(6707):184-6
references.pmid: 9823900
references.citation: Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59
references.pmid: 10839822
references.citation: Nature. 1998 Dec 10;396(6711):594-8
references.pmid: 9859997
references.citation: Br J Cancer. 2006 Sep 4;95(5):555-60
references.pmid: 16880778
references.citation: Cell. 1989 Jan 13;56(1):67-75
references.pmid: 2521301
references.citation: J Virol. 2005 May;79(9):5594-605
references.pmid: 15827174
references.citation: J Biol Chem. 2009 Dec 11;284(50):34793-808
references.pmid: 19828458
references.citation: Trends Biochem Sci. 1996 Jan;21(1):11-13
references.pmid: 8848831
references.citation: Cancer Res. 2007 Apr 1;67(7):3422-30
references.pmid: 17409453
references.citation: Mol Cell Biol. 2004 Apr;24(8):3404-14
references.pmid: 15060161
references.citation: J Biol Chem. 1998 Nov 27;273(48):31853-9
references.pmid: 9822653
references.citation: J Biol Chem. 2000 Jul 28;275(30):22986-94
references.pmid: 10816582
references.citation: J Biol Chem. 2000 Jul 7;275(27):20853-60
references.pmid: 10779504
references.citation: Mol Hum Reprod. 2008 Feb;14(2):107-16
references.pmid: 18048459
references.citation: J Biol Chem. 1994 May 6;269(18):13115-23
references.pmid: 8175737
references.citation: Cell. 1999 Sep 3;98(5):675-86
references.pmid: 10490106
references.citation: Cell. 1996 May 3;85(3):403-14
references.pmid: 8616895
references.citation: J Mol Endocrinol. 2005 Feb;34(1):107-18
references.pmid: 15691881
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2122-7
references.pmid: 9482849
references.citation: Cell. 1996 Nov 29;87(5):953-9
references.pmid: 8945521
references.citation: J Biol Chem. 1999 Sep 3;274(36):25756-68
references.pmid: 10464314
references.citation: Mol Cell Biol. 2001 Jan;21(1):39-50
references.pmid: 11113179
references.citation: Mol Cell Biol. 2003 Mar;23(6):2135-50
references.pmid: 12612084
references.citation: J Biol Chem. 2002 Mar 22;277(12):10226-35
references.pmid: 11779876
references.citation: Biochim Biophys Acta. 2002 Oct 21;1592(2):205-11
references.pmid: 12379484
references.citation: J Biol Chem. 1999 Dec 24;274(52):37219-25
references.pmid: 10601285
references.citation: Oncogene. 2004 May 24;23(24):4225-31
references.pmid: 15156177
references.citation: Genes Dev. 2000 Jul 1;14(13):1553-77
references.pmid: 10887150
references.citation: Trends Biochem Sci. 1997 May;22(5):151-3
references.pmid: 9175470
references.citation: J Biol Chem. 2004 Apr 2;279(14):14055-64
references.pmid: 14722092
references.citation: Mol Cell Biol. 2008 Mar;28(6):1947-63
references.pmid: 18212060
references.citation: Nucleic Acids Res. 1992 May 25;20(10):2603
references.pmid: 1350857
references.citation: J Biol Chem. 2007 Sep 14;282(37):27215-27228
references.pmid: 17623675
references.citation: Science. 2003 Apr 11;300(5617):342-4
references.pmid: 12690203
references.citation: J Cell Physiol. 1999 Nov;181(2):218-30
references.pmid: 10497301
references.citation: Cell. 1997 Aug 22;90(4):595-606
references.pmid: 9288740
references.citation: Cell. 1998 Jan 9;92(1):5-8
references.pmid: 9489694
references.citation: J Biol Chem. 2002 Jul 12;277(28):25631-9
references.pmid: 12000757
references.citation: Mol Cell. 1998 Oct;2(4):405-15
references.pmid: 9809062
references.citation: EMBO Rep. 2003 Oct;4(10):944-7
references.pmid: 14528264
references.citation: J Biol Chem. 2001 Apr 27;276(17):13505-8
references.pmid: 11279224
references.citation: Mol Cell. 2004 Nov 5;16(3):425-38
references.pmid: 15525515
references.citation: Cell Cycle. 2005 Jul;4(7):930-9
references.pmid: 15917652
references.citation: Cell. 1999 Feb 5;96(3):393-403
references.pmid: 10025405
references.citation: Nature. 1996 Dec 19-26;384(6610):641-3
references.pmid: 8967953
references.citation: J Biol Chem. 1998 Jan 2;273(1):92-101
references.pmid: 9417052
references.citation: Mol Endocrinol. 1995 Feb;9(2):208-18
references.pmid: 7776971
references.citation: EMBO J. 1998 Jan 15;17(2):507-19
references.pmid: 9430642