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The Laboratories for Reproductive Biology Departments of
Pediatrics (J.-A.T., S.S.H., K.G.H., F.S.F.) and Cell Biology (G.G.,
P.P.) University of North Carolina School of Medicine Chapel
Hill, North Carolina 27599-7500
Department of Biochemistry
(J.L.) and Departments of Medicine and Biochemistry (K.S.)
University of California Los Angeles, California 90095-1678
An androgen receptor (AR) interacting protein was isolated from a HeLa cell cDNA library by two-hybrid screening in yeast using the AR DNA+ligand binding domains as bait. The protein has sequence identity with human protein inhibitor of activated signal transducer and activator of transcription (PIAS1) and human Gu RNA helicase II binding protein (GBP). Binding of PIAS1 to human AR DNA+ligand binding domains was androgen dependent in the yeast liquid ß-galactosidase assay. Activation of binding by dihydrotestosterone was greater than testosterone > estradiol > progesterone. PIAS1 binding to full-length human AR in a reversed yeast two hybrid system was also androgen dependent. [35S] PIAS1 bound a glutathione S-transferase-AR-DNA binding domain (amino acids 544–634) fusion protein in affinity matrix assays. In transient cotransfection assays using CV1 cells with full-length human AR and a mouse mammary tumor virus luciferase reporter vector, there was an androgen-dependent 3- to 5-fold greater increase in luciferase activity with PIAS1 over that obtained with an equal amount of control antisense cDNA or mutant PIAS1. Constitutive transcriptional activity of the AR N-terminal+DNA binding domain was increased 6-fold by PIAS1. PIAS1 also enhanced glucocorticoid receptor transactivation in response to dexamethasone but inhibited progesterone-induced progesterone receptor transactivation in the same assay system. mRNA for PIAS1 was highly expressed in testis of human, monkey, rat, and mouse. In rat testis the onset of PIAS1 mRNA expression coincided with the initiation of spermatogenesis between 25–30 days of age. Immunostaining of human and mouse testis with PIAS1-specific antiserum demonstrated coexpression of PIAS1 with AR in Sertoli cells and Leydig cells. In addition, PIAS1 was expressed in spermatogenic cells. The results suggest that PIAS1 functions in testis as a nuclear receptor transcriptional coregulator and may have a role in AR initiation and maintenance of spermatogenesis.
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Z.-x. Zhou, B. He, S. H. Hall, E. M. Wilson, and F. S. French Domain Interactions between Coregulator ARA70 and the Androgen Receptor (AR) Mol. Endocrinol., February 1, 2002; 16(2): 287 - 300. [Abstract] [Full Text] [PDF]
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J. Liao, Y. Fu, and K. Shuai Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction PNAS, May 9, 2000; 97(10): 5267 - 5272. [Abstract] [Full Text] [PDF]
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T. Megidish, J. H. Xu, and C. W. Xu Activation of p53 by Protein Inhibitor of Activated Stat1 (PIAS1) J. Biol. Chem., March 1, 2002; 277(10): 8255 - 8259. [Abstract] [Full Text] [PDF]
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B. He, J. A. Kemppainen, and E. M. Wilson FXXLF and WXXLF Sequences Mediate the NH2-terminal Interaction with the Ligand Binding Domain of the Androgen Receptor J. Biol. Chem., July 21, 2000; 275(30): 22986 - 22994. [Abstract] [Full Text] [PDF]
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B. Liu and K. Shuai Induction of Apoptosis by Protein Inhibitor of Activated Stat1 through c-Jun NH2-terminal Kinase Activation J. Biol. Chem., September 21, 2001; 276(39): 36624 - 36631. [Abstract] [Full Text] [PDF]
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K. Takahashi, T. Taira, T. Niki, C. Seino, S. M. M. Iguchi-Ariga, and H. Ariga DJ-1 Positively Regulates the Androgen Receptor by Impairing the Binding of PIASxalpha to the Receptor J. Biol. Chem., September 28, 2001; 276(40): 37556 - 37563. [Abstract] [Full Text] [PDF]
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L.-N. Song, B. Huse, S. Rusconi, and S. S. Simons Jr. Transactivation Specificity of Glucocorticoid Versus Progesterone Receptors. ROLE OF FUNCTIONALLY DIFFERENT INTERACTIONS OF TRANSCRIPTION FACTORS WITH AMINO- AND CARBOXYL-TERMINAL RECEPTOR DOMAINS J. Biol. Chem., June 29, 2001; 276(27): 24806 - 24816. [Abstract] [Full Text] [PDF]
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L. H. Wang, X. Y. Yang, K. Mihalic, W. Xiao, D. Li, and W. L. Farrar Activation of Estrogen Receptor Blocks Interleukin-6-inducible Cell Growth of Human Multiple Myeloma Involving Molecular Cross-talk between Estrogen Receptor and STAT3 Mediated by Co-regulator PIAS3 J. Biol. Chem., August 17, 2001; 276(34): 31839 - 31844. [Abstract] [Full Text] [PDF]
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B. Saville, H. Poukka, M. Wormke, O. A. Janne, J. J. Palvimo, M. Stoner, I. Samudio, and S. Safe Cooperative Coactivation of Estrogen Receptor alpha in ZR-75 Human Breast Cancer Cells by SNURF and TATA-binding Protein J. Biol. Chem., January 18, 2002; 277(4): 2485 - 2497. [Abstract] [Full Text] [PDF]
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