{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T09:58:11Z","timestamp":1760781491527},"reference-count":37,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: Recent imaging studies revealed that androgen receptor (AR) is ligand-dependently translocated from the cytoplasm into the nucleus and forms intranuclear fine foci. In this study, we examined whether intracellular dynamics of mutant ARs detected in two androgen insensitivity syndrome (AIS) patients was impaired.<\/jats:p><jats:p>Objective: ARs with mutations in the DNA-binding domain were functionally characterized and compared with the wild-type AR.<\/jats:p><jats:p>Patients: In a complete AIS patient (subject 1), cysteine residue 579 in the first zinc finger motif of AR was substituted for phenylalanine (AR-C579F). Another mutation (AR-F582Y) was found in a partial AIS patient (subject 2).<\/jats:p><jats:p>Results: AR-F582Y retained less than 10% of the transactivation activity of the wild-type AR, whereas no ligand-dependent transactivation was detected for AR-C579F. Image analyses of the receptors fused to green fluorescent protein showed that the wild-type AR was ligand-dependently translocated into the nucleus in which it formed fine subnuclear foci. Surprisingly, after the addition of dihydrotestosterone, the two mutant ARs initially formed large cytoplasmic dots, many of which were found to be close to mitochondria by electron microscopy. Subsequently, a part of the ligand-bound mutant ARs gradually entered the nucleus to form a smaller number of larger dots, compared with the wild-type AR. Fluorescence recovery after photobleaching analysis revealed that the intranuclear mobility of the mutant ARs decreased, compared with that of the wild-type AR.<\/jats:p><jats:p>Conclusions: These results suggest that the abnormal translocation, localization, and mobility of the mutant ARs may be the cause of AIS in these subjects.<\/jats:p>","DOI":"10.1210\/jc.2005-0179","type":"journal-article","created":{"date-parts":[[2005,11,8]],"date-time":"2005-11-08T00:27:48Z","timestamp":1131409668000},"page":"6162-6169","source":"Crossref","is-referenced-by-count":21,"title":["Impaired Nuclear Translocation, Nuclear Matrix Targeting, and Intranuclear Mobility of Mutant Androgen Receptors Carrying Amino Acid Substitutions in the Deoxyribonucleic Acid-Binding Domain Derived from Androgen Insensitivity Syndrome Patients"],"prefix":"10.1210","volume":"90","author":[{"given":"Hisaya","family":"Kawate","sequence":"first","affiliation":[{"name":"Departments of Geriatric Medicine (H.K., Y.W., K.O., R.-H.T., R.T.), Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Geriatric Medicine (H.K., Y.W., K.O., R.-H.T., R.T.), Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keizo","family":"Ohnaka","sequence":"additional","affiliation":[{"name":"Departments of Geriatric Medicine (H.K., Y.W., K.O., R.-H.T., R.T.), Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-Hua","family":"Tao","sequence":"additional","affiliation":[{"name":"Departments of Geriatric Medicine (H.K., Y.W., K.O., R.-H.T., R.T.), Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei-ichiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of the Second Anatomy (K.N.), Kurume University School of Medicine, Kurume, 830-0011, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taijiro","family":"Okabe","sequence":"additional","affiliation":[{"name":"Medicine and Bioregulatory Science (T.O., T.Y., H.N.), Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Yanase","sequence":"additional","affiliation":[{"name":"Medicine and Bioregulatory Science (T.O., T.Y., H.N.), Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Nawata","sequence":"additional","affiliation":[{"name":"Medicine and Bioregulatory Science (T.O., T.Y., H.N.), Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Takayanagi","sequence":"additional","affiliation":[{"name":"Departments of Geriatric Medicine (H.K., Y.W., K.O., R.-H.T., R.T.), Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071616435324100_R1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0303-7207(02)00364-7","article-title":"Molecular action of androgens.","volume":"198","author":"Gobinet","year":"2002","journal-title":"Mol Cell Endocrinol"},{"key":"2020071616435324100_R2","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1152\/physrev.2001.81.3.1269","article-title":"Nuclear hormone receptors and gene expression.","volume":"81","author":"Aranda","year":"2001","journal-title":"Physiol Rev"},{"key":"2020071616435324100_R3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0303-7207(01)00466-X","article-title":"Molecular basis of androgen insensitivity.","volume":"179","author":"Brinkmann","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"2020071616435324100_R4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1749-6632.2001.tb04001.x","article-title":"Androgen receptor: structural domains and functional dynamics after ligand-receptor interaction.","volume":"949","author":"Roy","year":"2001","journal-title":"Ann NY Acad Sci"},{"key":"2020071616435324100_R5","doi-asserted-by":"crossref","first-page":"28395","DOI":"10.1074\/jbc.M101755200","article-title":"The subnuclear three-dimensional image analysis of androgen receptor fused to green fluorescence protein.","volume":"276","author":"Tomura","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071616435324100_R6","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1210\/mend.16.4.0812","article-title":"The presence of both the amino- and carboxyl-terminal domains in the AR is essential for the completion of a transcriptionally active form with coactivators and intranuclear compartmentalization common to the steroid hormone receptors: a three-dimensional imaging study.","volume":"16","author":"Saitoh","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071616435324100_R7","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1200\/JCO.2002.10.018","article-title":"Molecular biology of the androgen receptor.","volume":"20","author":"Gelmann","year":"2002","journal-title":"J Clin Oncol"},{"key":"2020071616435324100_R8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0039-128X(96)00015-3","article-title":"A clinician looks at androgen resistance.","volume":"61","author":"Balducci","year":"1996","journal-title":"Steroids"},{"key":"2020071616435324100_R9","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/(SICI)1096-8628(19991229)89:4<210::AID-AJMG5>3.0.CO;2-P","article-title":"Androgen insensitivity.","volume":"89","author":"Gottlieb","year":"1999","journal-title":"Am J Med Genet"},{"key":"2020071616435324100_R10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0303-7207(02)00369-6","article-title":"Androgen receptor mutations and androgen insensitivity.","volume":"198","author":"McPhaul","year":"2002","journal-title":"Mol Cell Endocrinol"},{"key":"2020071616435324100_R11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0303-7207(96)03812-9","article-title":"Androgen insensitivity syndrome due to new mutations in the DNA-binding domain of the androgen receptor.","volume":"120","author":"Imasaki","year":"1996","journal-title":"Mol Cell Endocrinol"},{"key":"2020071616435324100_R12","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.bbrc.2005.04.024","article-title":"A zinc finger protein TZF is a novel corepressor of androgen receptor.","volume":"331","author":"Ishizuka","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071616435324100_R13","first-page":"1152","article-title":"A single amino acid substitution (Met786\u2013Val) in the steroid-binding domain of human androgen receptor leads to complete androgen insensitivity syndrome.","volume":"74","author":"Nakao","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616435324100_R14","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1056\/NEJM200009213431205","article-title":"Androgen-insensitivity syndrome as a possible coactivator disease.","volume":"343","author":"Adachi","year":"2000","journal-title":"N Engl J Med"},{"key":"2020071616435324100_R15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.mce.2004.10.009","article-title":"Tob proteins suppress steroid hormone receptor-mediated transcriptional activation.","volume":"230","author":"Kawate","year":"2005","journal-title":"Mol Cell Endocrinol"},{"key":"2020071616435324100_R16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/002215540305100301","article-title":"Visualization of identified GFP-expressing cells by light and electron microscopy.","volume":"51","author":"Luby-Phelps","year":"2003","journal-title":"J Histochem Cytochem"},{"key":"2020071616435324100_R17","doi-asserted-by":"crossref","first-page":"5263","DOI":"10.1093\/nar\/16.12.5263","article-title":"Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus.","volume":"16","author":"Ham","year":"1988","journal-title":"Nucleic Acids Res"},{"key":"2020071616435324100_R18","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1679\/aohc.64.353","article-title":"Subcellular steroid\/nuclear receptor dynamics.","volume":"64","author":"Kawata","year":"2001","journal-title":"Arch Histol Cytol"},{"key":"2020071616435324100_R19","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1210\/mend.16.7.0880","article-title":"Navigating steroid hormone receptors through the nuclear compartment.","volume":"16","author":"DeFranco","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071616435324100_R20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbaexp.2003.09.016","article-title":"Dynamics of nuclear receptor movement and transcription.","volume":"1677","author":"Hager","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"2020071616435324100_R21","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/hmg\/8.5.731","article-title":"Polyglutamine-expanded androgen receptors from aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone.","volume":"8","author":"Stenoien","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2020071616435324100_R22","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1091\/mbc.12.5.1393","article-title":"Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation.","volume":"12","author":"Waelter","year":"2001","journal-title":"Mol Biol Cell"},{"key":"2020071616435324100_R23","doi-asserted-by":"crossref","first-page":"34462","DOI":"10.1074\/jbc.M205420200","article-title":"Aggregation of misfolded proteins can be a selective process dependent upon peptide composition.","volume":"277","author":"Milewski","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071616435324100_R24","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1096\/fj.01-1035fje","article-title":"Androgen receptor with elongated polyglutamine tract forms aggregates that alter axonal trafficking and mitochondrial distribution in motoneuronal processes.","volume":"16","author":"Piccioni","year":"2002","journal-title":"FASEB J"},{"key":"2020071616435324100_R25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/35050515","article-title":"FRAP reveals that mobility of oestrogen receptor-\u03b1 is ligand- and proteasome-dependent.","volume":"3","author":"Stenoien","year":"2001","journal-title":"Nat Cell Biol"},{"key":"2020071616435324100_R26","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1128\/MCB.23.6.1922-1934.2003","article-title":"Molecular determinants of glucocorticoid receptor mobility in living cells: the importance of ligand affinity.","volume":"23","author":"Schaaf","year":"2003","journal-title":"Mol Cell Biol"},{"key":"2020071616435324100_R27","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1074\/jbc.M202752200","article-title":"Dynamic shuttling and intranuclear mobility of nuclear hormone receptors.","volume":"278","author":"Maruvada","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071616435324100_R28","first-page":"518","article-title":"Subnuclear trafficking of estrogen receptor-\u03b1 and steroid receptor coactivator-1.","volume":"14","author":"Stenoien","year":"2000","journal-title":"Mol Endocrinol"},{"key":"2020071616435324100_R29","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.1016\/S0021-9258(17)37410-0","article-title":"Glucocorticoid receptors in ATP-depleted cells. Dephosphorylation, loss of hormone binding, HSP90 dissociation, and ATP-dependent cycling.","volume":"269","author":"Hu","year":"1994","journal-title":"J Biol Chem"},{"key":"2020071616435324100_R30","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1128\/MCB.16.5.1989","article-title":"ATP-dependent release of glucocorticoid receptors from the nuclear matrix.","volume":"16","author":"Tang","year":"1996","journal-title":"Mol Cell Biol"},{"key":"2020071616435324100_R31","first-page":"3597","article-title":"Trafficking of androgen receptor mutants fused to green fluorescent protein: a new investigation of partial androgen insensitivity syndrome.","volume":"83","author":"Georget","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616435324100_R32","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1210\/mend.13.12.0382","article-title":"A C619Y mutation in the human androgen receptor causes inactivation and mislocalization of the receptor with concomitant sequestration of SRC-1 (steroid receptor coactivator 1).","volume":"13","author":"Nazareth","year":"1999","journal-title":"Mol Endocrinol"},{"key":"2020071616435324100_R33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0014-5793(02)02929-0","article-title":"Pure antiandrogens disrupt the recruitment of coactivator GRIP1 to colocalize with androgen receptor in nuclei.","volume":"523","author":"Karvonen","year":"2002","journal-title":"FEBS Lett"},{"key":"2020071616435324100_R34","doi-asserted-by":"crossref","first-page":"8389","DOI":"10.1074\/jbc.M311761200","article-title":"Androgen receptor acetylation site mutations cause trafficking defects, misfolding, and aggregation similar to expanded glutamine tracts.","volume":"279","author":"Thomas","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071616435324100_R35","doi-asserted-by":"crossref","first-page":"20853","DOI":"10.1074\/jbc.M000660200","article-title":"p300 and p300\/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation.","volume":"275","author":"Fu","year":"2000","journal-title":"J Biol Chem"},{"key":"2020071616435324100_R36","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S0092-8674(03)00934-6","article-title":"Estrogen receptor-\u03b1 directs ordered, cyclical, and combinational recruitment of cofactors on a natural target promoter.","volume":"115","author":"Me\u0301tivier","year":"2003","journal-title":"Cell"},{"key":"2020071616435324100_R37","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.287.5456.1262","article-title":"The glucocorticoid receptor: rapid exchange with regulatory sites in living cells.","volume":"287","author":"McNally","year":"2000","journal-title":"Science"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/11\/6162\/10777889\/jcem6162.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/11\/6162\/10777889\/jcem6162.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T08:59:54Z","timestamp":1626685194000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/90\/11\/6162\/2838459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,1]]},"references-count":37,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2005,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2005-0179","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,1]]}}}