title: Cyclin D3/CDK11p58 complex is involved in the repression of androgen receptor.
abstract: Androgen receptor (AR) is essential for the maintenance of the male reproductive systems and is critical for the carcinogenesis of human prostate cancers (PCas). D-type cyclins are closely related to the repression of AR function. It has been well documented that cyclin D1 inhibits AR function through multiple mechanisms, but the mechanism of how cyclin D3 exerts its repressive role in the AR signaling pathway remains to be identified. In the present investigation, we demonstrate that cyclin D3 and the 58-kDa isoform of cyclin-dependent kinase 11 (CDK11p58) repressed AR transcriptional activity as measured by reporter assays of transformed cells and prostate-specific antigen expression in PCa cells. AR, cyclin D3, and CDK11p58 formed a ternary complex in cells and were colocalized in the luminal epithelial layer of the prostate. AR activity is controlled by phosphorylation at specific sites. We found that AR was phosphorylated at Ser-308 by cyclin D3/CDK11p58 in vitro and in vivo, leading to the repressed activity of AR transcriptional activation unit 1 (TAU1). Furthermore, androgen-dependent proliferation of PCa cells was inhibited by cyclin D3/CDK11p58 through AR repression. These data suggest that cyclin D3/CDK11p58 signaling is involved in the negative regulation of AR function.
authors: Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Gene Research Center, Shanghai Medical College, Shanghai 200032, People's Republic of China.
authors: Hongliang
authors: H
authors: Zong
authors: Yayun
authors: Y
authors: Chi
authors: Yanlin
authors: Y
authors: Wang
authors: Yanzhong
authors: Y
authors: Yang
authors: Li
authors: L
authors: Zhang
authors: Haijiao
authors: H
authors: Chen
authors: Jianhai
authors: J
authors: Jiang
authors: Zejuan
authors: Z
authors: Li
authors: Yi
authors: Y
authors: Hong
authors: Hanzhou
authors: H
authors: Wang
authors: Xiaojing
authors: X
authors: Yun
authors: Jianxin
authors: J
authors: Gu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D056743:Cyclin D3; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D046912:Multiprotein Complexes; D020033:Protein Isoforms; D011944:Receptors, Androgen; D012694:Serine; D018844:Cyclin-Dependent Kinases; D017430:Prostate-Specific Antigen
references: J Biol Chem. 2003 Mar 7;278(10):8623-9
references: 12501247
references: Cancer Genet Cytogenet. 1999 Jan 15;108(2):120-6
references: 9973938
references: Cancer Cell Int. 2005 Apr 06;5(1):8
references: 15813967
references: J Biol Chem. 2004 Apr 30;279(18):19191-200
references: 14985354
references: Oncogene. 1998 Aug 27;17(8):1027-37
references: 9747882
references: FEBS Lett. 2005 Jul 4;579(17):3579-88
references: 15963510
references: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7200-5
references: 11404460
references: Mol Cell. 2000 Apr;5(4):597-605
references: 10882096
references: Cancer Res. 1999 May 15;59(10):2297-301
references: 10344732
references: Biochem J. 1996 Nov 1;319 ( Pt 3):657-67
references: 8920964
references: Cancer Genet Cytogenet. 2001 Jul 15;128(2):181-2
references: 11478303
references: Cancer Res. 1991 Oct 1;51(19):5165-70
references: 1913642
references: J Biol Chem. 2001 Mar 16;276(11):8475-83
references: 11110801
references: J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):91-9
references: 9699861
references: Cancer Lett. 2007 Aug 28;254(1):137-45
references: 17433535
references: Mol Endocrinol. 1991 Oct;5(10):1396-404
references: 1775129
references: Expert Rev Anticancer Ther. 2005 Feb;5(1):63-74
references: 15757439
references: J Steroid Biochem Mol Biol. 1997 Jul;62(4):233-42
references: 9408077
references: Mol Cell Biol. 1995 Jan;15(1):1-11
references: 7528324
references: Prostate. 2005 May 1;63(2):117-30
references: 15486994
references: Cell. 2000 Apr 28;101(3):243-5
references: 10847679
references: Mol Endocrinol. 2005 Mar;19(3):607-20
references: 15539430
references: Crit Rev Eukaryot Gene Expr. 1995;5(2):97-125
references: 8845584
references: Endocr Rev. 2004 Apr;25(2):276-308
references: 15082523
references: Nat Genet. 2004 Jun;36(6):618-23
references: 15133513
references: Nature. 2005 Sep 15;437(7057):436-9
references: 16079795
references: CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30
references: 16514137
references: Mol Endocrinol. 1997 Jun;11(6):823-32
references: 9171245
references: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5458-63
references: 10318905
references: Mol Endocrinol. 2000 Oct;14(10):1603-17
references: 11043576
references: Mol Endocrinol. 2001 May;15(5):797-811
references: 11328859
references: Mol Biol Cell. 1998 Sep;9(9):2527-43
references: 9725910
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5156-61
references: 15790678
references: Mol Endocrinol. 2006 Mar;20(3):503-15
references: 16282370
references: EMBO Rep. 2006 Apr;7(4):418-24
references: 16462731
references: Biochem Soc Trans. 2003 Oct;31(Pt 5):1042-6
references: 14505476
references: Nat Genet. 1994 Jul;7(3):370-5
references: 7920654
references: J Biol Chem. 1994 Jun 3;269(22):15786-94
references: 8195233
references: J Biol Chem. 2002 Jan 18;277(3):2207-15
references: 11714699
references: Biochem Biophys Res Commun. 2001 Jun 15;284(3):836-44
references: 11396978
references: Mol Cell Biol. 1999 Sep;19(9):6085-97
references: 10454556
references: J Biol Chem. 1998 Aug 7;273(32):20213-22
references: 9685369
references: Mol Endocrinol. 1995 May;9(5):605-15
references: 7565807
references: FEBS Lett. 2004 Aug 27;573(1-3):139-46
references: 15327989
references: J Biol Chem. 2002 Sep 20;277(38):35314-22
references: 12082095
references: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7467-71
references: 2217177
references: J Biol Chem. 1991 Apr 25;266(12):7549-55
references: 2019585
references: J Biol Chem. 2006 Sep 22;281(38):27882-93
references: 16870607
references: J Biol Chem. 2002 Aug 9;277(32):29304-14
references: 12015328
references: J Biol Chem. 1999 Aug 6;274(32):22296-302
references: 10428798
references: J Cell Biol. 2000 Aug 21;150(4):873-80
references: 10953010
references: Cancer Res. 1983 Apr;43(4):1809-18
references: 6831420
references: Genes Chromosomes Cancer. 1996 May;16(1):15-20
references: 9162192
references: Mol Cell Biol. 2005 Jan;25(1):264-77
references: 15601848
references: Endocr Res. 1996 Aug;22(3):197-219
references: 8875135
references: Int J Gynecol Cancer. 2006 Jul-Aug;16(4):1668-72
references: 16884382
references: Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15969-74
references: 17043241
references: J Biol Chem. 2000 Nov 10;275(45):35200-8
references: 10930412
references: Science. 1988 Apr 15;240(4850):324-6
references: 3353726
references: J Biol Chem. 2002 Jan 25;277(4):2589-96
references: 11709559
references: Mol Cell Biol. 2005 Feb;25(4):1425-36
references: 15684393
references: Cancer Genet Cytogenet. 1999 Jan 15;108(2):91-9
references: 9973934