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Gene Review

AR  -  androgen receptor

Homo sapiens

Synonyms: AIS, Androgen receptor, DHTR, Dihydrotestosterone receptor, HUMARA, ...
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Disease relevance of AR


Psychiatry related information on AR


High impact information on AR


Chemical compound and disease context of AR

  • Mutations or abnormal expression of AR in prostate cancer can play a key role in the process that changes prostate cancer from androgen-dependent to an androgen-independent stage [15].
  • Using a yeast two-hybrid system, we were able to isolate a ligand-dependent AR-associated protein (ARA70), which functions as an activator to enhance AR transcriptional activity 10-fold in the presence of 10(-10) M dihydrotestosterone or 10(-9) M testosterone, but not 10(-6) M hydroxyflutamide in human prostate cancer DU145 cells [15].
  • Ligand-dependent activation of the AR in human T47D and MCF-7 breast cancer cells resulted in inhibition of estradiol-stimulated cell proliferation and a reduction in the capacity of the ER to induce expression of the PR [16].
  • CONCLUSION: Response to MPA after adjuvant tamoxifen treatment for lymph node-positive breast cancer was positively associated with AR level in the primary tumor [3].
  • Here we apply the phage display technique to identify some new signature motifs, (F/W)XXL(F/W) and FXXLY (where F is phenylalanine, W is tryptophan, L is leucine, Y is tyrosine, and X is any amino acid) that can influence the interaction between AR and AR coregulators [17].

Biological context of AR

  • Beta-catenin acts as a coactivator of AR transcription and is also involved in co-trafficking, increasing cell proliferation, and prostate pathogenesis [18].
  • AR regulation of the prostate specific antigen (PSA) gene involves both a promoter-proximal sequence as well as an enhancer approximately 4 kb upstream [1].
  • Here we report that, in contrast to estrogen receptor transcription complexes which form within minutes and recycle hourly, the levels of regulatory regions bound by AR complexes rise over a 16 hr period and then slowly decline [1].
  • We found a similar interaction between the SRD5A2 VV genotype and fewer AR gene CAG repeats (OR = 5.58; 95% CI = 1.86 to 16.71) [19].
  • It has been shown that transcriptional activation of AR is regulated through interaction with various co-factors [20].

Anatomical context of AR


Associations of AR with chemical compounds

  • Importantly, PRK signalling also stimulates AR activity in the presence of adrenal androgens, which are still present in prostate tumour patients subjected to testicular androgen ablation therapy [22].
  • In an agonist- and AF-2-dependent manner FHL2 selectively increases the transcriptional activity of the AR, but not that of any other nuclear receptor [23].
  • Together, our data suggest, for the first time, testosterone/dihydrotestosterone may not be the only ligands for the AR [24].
  • Mammalian two-hybrid and glutathione S-transferase pull-down assays indicate a domain within SV (amino acids 594-1268) can interact with AR N terminus and DNA-binding domain-ligand-binding domain in a ligand-enhanced manner [21].
  • The AR is posttranslationally modified on lysine residues by acetylation and sumoylation [25].
  • A specific inhibitor to the DNA-dependent protein kinase, NU7026, inhibits androgen receptor export and phosphorylation [26].

Physical interactions of AR

  • The present study indicates that, in human prostate cancer cells, CDK6 can also bind to the androgen receptor (AR) and stimulate its transcriptional activity in the presence of dihydrotestosterone [27].
  • We previously identified LSD1 and FHL2 as nuclear cofactors interacting specifically with the AR in prostate cells and showed that both stimulate androgen-dependent gene transcription [28].
  • Whereas both the N terminus and ligand-binding domain of AR can interact with CBP, a short region in the N terminus of CBP is required for these interactions [29].
  • Yeast and mammalian two-hybrid systems and co-immunoprecipitation assays all prove ARA55 can bind to AR in a ligand-dependent manner [30].
  • The RU486-liganded AR interacted with a C-terminal fragment of NCoR, and this interaction was mediated by the two most C-terminal nuclear receptor interacting domains (RIDs) present in NCoR [31].

Enzymatic interactions of AR


Co-localisations of AR

  • Although full-length FLNa was predominantly cytoplasmic, a C-terminal 100-kDa fragment of FLNa colocalized with AR to the nucleus [37].
  • In human testis, immunostaining of SRC-3 colocalized with AR in nuclei of Sertoli cells and peritubular myoid cells, indicating it could function as an AR coactivator in these cells [38].
  • JMJD2C colocalizes with androgen receptor and LSD1 in normal prostate and in prostate carcinomas [39].

Regulatory relationships of AR

  • SV preferentially enhanced AR rather than other tested nuclear receptors and could be induced by natural androgens better than other steroids [21].
  • Consistent with previous reports, expression of cyclin D1a inhibited cell-cycle progression in AR-dependent prostate cancer cells [40].
  • Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions [37].
  • These findings suggest that CDK6 may play an important role in the development and/or progression of a subset of human prostate cancers by stimulating the activity of the AR [27].
  • MEKK1 induced AR-dependent apoptosis in prostate cancer cells [25].

Other interactions of AR


Analytical, diagnostic and therapeutic context of AR


  1. Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Wang, Q., Carroll, J.S., Brown, M. Mol. Cell (2005) [Pubmed]
  2. Human megakaryocytes and platelets contain the estrogen receptor beta and androgen receptor (AR): testosterone regulates AR expression. Khetawat, G., Faraday, N., Nealen, M.L., Vijayan, K.V., Bolton, E., Noga, S.J., Bray, P.F. Blood (2000) [Pubmed]
  3. Medroxyprogesterone acetate therapy in advanced breast cancer: the predictive value of androgen receptor expression. Birrell, S.N., Roder, D.M., Horsfall, D.J., Bentel, J.M., Tilley, W.D. J. Clin. Oncol. (1995) [Pubmed]
  4. Specificity of cyclin D1 for androgen receptor regulation. Petre-Draviam, C.E., Cook, S.L., Burd, C.J., Marshall, T.W., Wetherill, Y.B., Knudsen, K.E. Cancer Res. (2003) [Pubmed]
  5. BRCA2 germ-line mutations are frequent in male breast cancer patients without a family history of the disease. Haraldsson, K., Loman, N., Zhang, Q.X., Johannsson, O., Olsson, H., Borg, A. Cancer Res. (1998) [Pubmed]
  6. Sex steroid level, androgen receptor polymorphism, and depressive symptoms in healthy elderly men. T'Sjoen, G.G., De Vos, S., Goemaere, S., Van Pottelbergh, I., Dierick, M., Van Heeringen, C., Kaufman, J.M. Journal of the American Geriatrics Society. (2005) [Pubmed]
  7. Androgens, androgen receptors, and male gender role behavior. Wilson, J.D. Hormones and behavior. (2001) [Pubmed]
  8. Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling. Dong, Y., Lee, S.O., Zhang, H., Marshall, J., Gao, A.C., Ip, C. Cancer Res. (2004) [Pubmed]
  9. Association study of androgen receptor CAG repeat polymorphism and male violent criminal activity. Cheng, D., Hong, C.J., Liao, D.L., Tsai, S.J. Psychoneuroendocrinology (2006) [Pubmed]
  10. Sex steroid-related genes and male-to-female transsexualism. Henningsson, S., Westberg, L., Nilsson, S., Lundström, B., Ekselius, L., Bodlund, O., Lindström, E., Hellstrand, M., Rosmond, R., Eriksson, E., Landén, M. Psychoneuroendocrinology (2005) [Pubmed]
  11. Advances in prostate cancer chemotherapy: a new era begins. Pienta, K.J., Smith, D.C. CA: a cancer journal for clinicians. (2005) [Pubmed]
  12. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Kousteni, S., Bellido, T., Plotkin, L.I., O'Brien, C.A., Bodenner, D.L., Han, L., Han, K., DiGregorio, G.B., Katzenellenbogen, J.A., Katzenellenbogen, B.S., Roberson, P.K., Weinstein, R.S., Jilka, R.L., Manolagas, S.C. Cell (2001) [Pubmed]
  13. Monoclonal origin of multicentric Kaposi's sarcoma lesions. Rabkin, C.S., Janz, S., Lash, A., Coleman, A.E., Musaba, E., Liotta, L., Biggar, R.J., Zhuang, Z. N. Engl. J. Med. (1997) [Pubmed]
  14. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. Taplin, M.E., Bubley, G.J., Shuster, T.D., Frantz, M.E., Spooner, A.E., Ogata, G.K., Keer, H.N., Balk, S.P. N. Engl. J. Med. (1995) [Pubmed]
  15. Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Yeh, S., Chang, C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  16. Decreased androgen receptor levels and receptor function in breast cancer contribute to the failure of response to medroxyprogesterone acetate. Buchanan, G., Birrell, S.N., Peters, A.A., Bianco-Miotto, T., Ramsay, K., Cops, E.J., Yang, M., Harris, J.M., Simila, H.A., Moore, N.L., Bentel, J.M., Ricciardelli, C., Horsfall, D.J., Butler, L.M., Tilley, W.D. Cancer Res. (2005) [Pubmed]
  17. The use of phage display technique for the isolation of androgen receptor interacting peptides with (F/W)XXL(F/W) and FXXLY new signature motifs. Hsu, C.L., Chen, Y.L., Yeh, S., Ting, H.J., Hu, Y.C., Lin, H., Wang, X., Chang, C. J. Biol. Chem. (2003) [Pubmed]
  18. Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Mulholland, D.J., Dedhar, S., Coetzee, G.A., Nelson, C.C. Endocr. Rev. (2005) [Pubmed]
  19. Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men. Yu, M.W., Yang, Y.C., Yang, S.Y., Cheng, S.W., Liaw, Y.F., Lin, S.M., Chen, C.J. J. Natl. Cancer Inst. (2001) [Pubmed]
  20. hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci. Sharma, M., Li, X., Wang, Y., Zarnegar, M., Huang, C.Y., Palvimo, J.J., Lim, B., Sun, Z. EMBO J. (2003) [Pubmed]
  21. Supervillin associates with androgen receptor and modulates its transcriptional activity. Ting, H.J., Yeh, S., Nishimura, K., Chang, C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  22. A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer. Metzger, E., Müller, J.M., Ferrari, S., Buettner, R., Schüle, R. EMBO J. (2003) [Pubmed]
  23. FHL2, a novel tissue-specific coactivator of the androgen receptor. Müller, J.M., Isele, U., Metzger, E., Rempel, A., Moser, M., Pscherer, A., Breyer, T., Holubarsch, C., Buettner, R., Schüle, R. EMBO J. (2000) [Pubmed]
  24. From estrogen to androgen receptor: a new pathway for sex hormones in prostate. Yeh, S., Miyamoto, H., Shima, H., Chang, C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  25. Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Fu, M., Wang, C., Wang, J., Zhang, X., Sakamaki, T., Yeung, Y.G., Chang, C., Hopp, T., Fuqua, S.A., Jaffray, E., Hay, R.T., Palvimo, J.J., Jänne, O.A., Pestell, R.G. Mol. Cell. Biol. (2002) [Pubmed]
  26. Activation of the DNA-dependent protein kinase stimulates nuclear export of the androgen receptor in vitro. Shank, L.C., Kelley, J.B., Gioeli, D., Yang, C.S., Spencer, A., Allison, L.A., Paschal, B.M. J. Biol. Chem. (2008) [Pubmed]
  27. Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer cells. Lim, J.T., Mansukhani, M., Weinstein, I.B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  28. Androgen Receptor Coactivators Lysine-Specific Histone Demethylase 1 and Four and a Half LIM Domain Protein 2 Predict Risk of Prostate Cancer Recurrence. Kahl, P., Gullotti, L., Heukamp, L.C., Wolf, S., Friedrichs, N., Vorreuther, R., Solleder, G., Bastian, P.J., Ellinger, J., Metzger, E., Sch??le, R., Buettner, R. Cancer Res. (2006) [Pubmed]
  29. CREB binding protein is a coactivator for the androgen receptor and mediates cross-talk with AP-1. Frønsdal, K., Engedal, N., Slagsvold, T., Saatcioglu, F. J. Biol. Chem. (1998) [Pubmed]
  30. Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. Fujimoto, N., Yeh, S., Kang, H.Y., Inui, S., Chang, H.C., Mizokami, A., Chang, C. J. Biol. Chem. (1999) [Pubmed]
  31. The androgen receptor recruits nuclear receptor CoRepressor (N-CoR) in the presence of mifepristone via its N and C termini revealing a novel molecular mechanism for androgen receptor antagonists. Hodgson, M.C., Astapova, I., Cheng, S., Lee, L.J., Verhoeven, M.C., Choi, E., Balk, S.P., Hollenberg, A.N. J. Biol. Chem. (2005) [Pubmed]
  32. Mechanisms of endocrine therapy-responsive and -unresponsive prostate tumours. Culig, Z., Steiner, H., Bartsch, G., Hobisch, A. Endocr. Relat. Cancer (2005) [Pubmed]
  33. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Li, L., Ren, C.H., Tahir, S.A., Ren, C., Thompson, T.C. Mol. Cell. Biol. (2003) [Pubmed]
  34. Inhibition of androgen receptor-mediated transcription by amino-terminal enhancer of split. Yu, X., Li, P., Roeder, R.G., Wang, Z. Mol. Cell. Biol. (2001) [Pubmed]
  35. Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity. Salas, T.R., Kim, J., Vakar-Lopez, F., Sabichi, A.L., Troncoso, P., Jenster, G., Kikuchi, A., Chen, S.Y., Shemshedini, L., Suraokar, M., Logothetis, C.J., DiGiovanni, J., Lippman, S.M., Menter, D.G. J. Biol. Chem. (2004) [Pubmed]
  36. Functional analysis of a novel androgen receptor mutation, Q902K, in an individual with partial androgen insensitivity. Umar, A., Berrevoets, C.A., Van, N.M., van Leeuwen, M., Verbiest, M., Kleijer, W.J., Dooijes, D., Grootegoed, J.A., Drop, S.L., Brinkmann, A.O. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  37. Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions. Loy, C.J., Sim, K.S., Yong, E.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  38. Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator. Tan, J.A., Hall, S.H., Petrusz, P., French, F.S. Endocrinology (2000) [Pubmed]
  39. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Wissmann, M., Yin, N., Müller, J.M., Greschik, H., Fodor, B.D., Jenuwein, T., Vogler, C., Schneider, R., Günther, T., Buettner, R., Metzger, E., Schüle, R. Nat. Cell Biol. (2007) [Pubmed]
  40. Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation. Burd, C.J., Petre, C.E., Morey, L.M., Wang, Y., Revelo, M.P., Haiman, C.A., Lu, S., Fenoglio-Preiser, C.M., Li, J., Knudsen, E.S., Wong, J., Knudsen, K.E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  41. Expression of human estrogen receptor-alpha and -beta, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. Lau, K.M., Mok, S.C., Ho, S.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  42. Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Latil, A., Bièche, I., Vidaud, D., Lidereau, R., Berthon, P., Cussenot, O., Vidaud, M. Cancer Res. (2001) [Pubmed]
  43. A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. Amir, A.L., Barua, M., McKnight, N.C., Cheng, S., Yuan, X., Balk, S.P. J. Biol. Chem. (2003) [Pubmed]
  44. Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3'-untranslated region of the androgen receptor messenger RNA. Yeap, B.B., Voon, D.C., Vivian, J.P., McCulloch, R.K., Thomson, A.M., Giles, K.M., Czyzyk-Krzeska, M.F., Furneaux, H., Wilce, M.C., Wilce, J.A., Leedman, P.J. J. Biol. Chem. (2002) [Pubmed]
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