Androgeni receptor

(Preusmjereno sa Receptor androgena)

Androgeni receptor (AR), poznat i kao NR3C4 (potporodica jedarnih receptora 3, grupa C, član 4), je tip jedarnih receptora[5] koji se aktivira vezanjem bilo kog od androgenih hormona, uključujući testosteron i dihidrotestosteron[6] u citoplazmi, a zatim se translocira u jedro. Receptor androgena je u najbližoj vezi sa progesteronskim receptorom, a progestin u većim dozama može blokirati androgeni receptor.[7][8]

Androgeni receptor
Identifikatori
SimbolAR
Alt. simboliAR, AIS, AR8, DHTR, HUMARA, HYSP1, KD, NR3C4, SBMA, SMAX1, TFM, androgen receptor
Raspon tkivne ekspresije gena AC
OMIM313700
Ortolozi28
UniProt[https://www.uniprot.org/uniprot/P10275

Q9NUA2 P10275

Q9NUA2]
Ostali podaci
LokusHrom. X [https://omim.org/search/?index=geneMap&search=Xq

Band =Xq12{{{bend}}} q

Band =Xq12{{{bend}}}{{{lokus_dopunski_podaci}}}]
Pretraga za
Strukture[https://swissmodel.expasy.org/repository/uniprot/P10275
Q9NUA2 Swiss-model]
Domene[https://www.ebi.ac.uk/interpro/protein/P10275
Q9NUA2 InterPro]
Kod čovjeka, gen AR nalazi se na dugom (q) kraku X-hromosoma, pozicija Xq12
Androgeni receptor
Kristalna struktura domena vezanja liganda ljudskog androgenih receptora vezana za nh2-terminalni peptid androgenih receptora ar20-30 i r1881
Identifikatori
SimbolAR
Normalna funkcija androgenog receptora.
Testosteron (T) ulazi u ćeliju i, ako je prisutna 5-alfa-reduktaza, pretvara se u dihidrotestosteron (DHT).
Nakon vezanja steroida, androgeni receptor (AR) prolazi kroz konformacijsku promjenu i oslobađa proteine toplotnog šoka (hsps).
Fosforilacija (P) se javlja prije ili poslije vezanja steroida.
AR se translocira u jedro, gdje dolazi do dimerizacije, vezivanja DNK i regrutacije koaktivatora.
Ciljni geni se transkribiraju (mRNA) i prevode u proteine.[1][2][3][4]

Glavna funkcija receptora androgena je vezanje DNK faktora transkripcije koji regulira ekspresiju gena;[9] međutim, androgeni receptor ima i druge funkcije.[10] Geni regulirani androgenom kritični su za razvoj i održavanje muškog spolnog fenotipa.

Funkcija uredi

Efekti na razvoj uredi

U nekim tipovima ćelija, testosteron direktno komunicira sa androgenim receptorima, dok ga u drugim 5-alfa reduktaza pretvara u dihidrotestosteron, još snažniji agonist za aktivaciju androgenih receptora.[11] Testosteron se javlja kao primarni hormon koji aktivira androgene receptore u Wolffovom kanalu, dok je dihidrotestosteron glavni androgeni hormon u urogenitalnom sinusu, urogenitalnom tuberkulumu i dlakinim folikulima.[12] Testosteron je stoga odgovoran prvenstveno za razvoj muških primarnih spolnih obilježja, dok je dihidrotestosteron odgovoran za sekundarne muške spolne karakteristike.

Androgeni uzrokuju sporo sazrijevanje kostiju, ali veći učinak snažnog sazrijevanja dolazi od estrogena proizvedenog aromatizacijom androgena. Korisnici steroida u tinejdžerskoj dobi mogu otkriti da je njihov rast zaustavio višak androgena i / ili estrogena. Ljudi s premalo spolnih hormona mogu biti niski tokom puberteta, ali na kraju su viši od prosjeka odraslih kao u sindromu neosjetljivosti na androgen ili sindromu neosjetljivosti na estrogen.[13]

Studije nokaut-miševa pokazale su da je androgeni receptor neophodan za normalnu plodnost žena, potreban za razvoj i punu funkcionalnost folikula jajnika i ovulacije, djelujući preko oba jajnika i neuroendokrinim mehanizmima.[14]

Održavanje integriteta muškog skeleta uredi

Preko androgenih receptora, androgeni imaju ključnu ulogu u održavanju integriteta muškog skeleta. Regulacija ovog integriteta signalizacijom androgenih receptora (AR) može se pripisati i osteoblastima i osteocitima.[15]

Uloga kod žena uredi

AR ima ulogu u regulaciji ženskih seksualnih, somatskih etoloških funkcija. Eksperimentalni podaci korištenjem AR knokout ženskih miševa pružaju dokaze da je promocija srčanog rasta, hipertrofije bubrega, rasta kortikalne kosti i regulacije trabekulske koštane strukture rezultat djelovanja ovisnih o DNK AR-a kod žena.

Štaviše, važnost razumijevanja ženskih androgenih receptora leži u njihovoj ulozi u nekoliko genetički kontroliranih poremećaja, uključujući sindrom neosjetljivosti na androgene (AIS). kompletni (CAIS) i djelimični (PAIS) koji su rezultat mutacije u genima koji kodiraju AR. Ove mutacije uzrokuju inaktivaciju AR-a, zbog mutacija koje daju otpor cirkulirajućem testosteronu, a prijavljeno je više od 400 različitih mutacija AR-a.

Mehanizam djelovanja uredi

Genomski uredi

Primarni mehanizam djelovanja za androgene receptore je direktna regulacija transkripcije gena. Vezanje androgena za androgeni receptor rezultira konformacijskom promjenom u receptoru, što zauzvrat uzrokuje disocijaciju proteina toplotnog šoka, transporta iz citosola u ćelijska jedra i dimerizaciju. Dimer androgenih receptora veže se za određenu sekvencu DNK poznatu kao element hormonskog odgovora. Androgeni receptori komuniciraju s drugim proteinima u jedru, što rezultira regulacijom prema gore ili dolje specifične transkripcije gena.[16] Povećana regulacija ili aktivacija transkripcije rezultira povećanom sintezom iRNK, koju prevode ribosomi da bi se proizveli specifični proteini. Jedan od poznatih ciljnih gena aktivacije androgenih receptora je insulinoliki receptor faktora rasta (IGF-1R).[17] Stoga su promjene nivoa specifičnih proteina u ćelijama jedan od načina na koji androgeni receptori kontroliraju ponašanje ćelija.

Jedna funkcija androgenih receptora koja je neovisna od direktnog vezanja za njegovu ciljnu sekvencu DNK olakšava se regrutacijom putem drugih DNK-vržućih proteina. Jedan od primjera je faktor odgovora u serumu, protein koji aktivira nekoliko gena koji uzrokuju rast mišića.[18]

Androgeni receptor se modificira u post-translacijskoj modifikaciji putem acetilacije,[19] koja direktno promovira transaktivaciju, apoptozu posredovanu AR-om[20] i rast ćelija kontaktno-neovisnog karcinoma prostate.[21] Acetilacija AR-a inducuranu pomoću androgena[22] određuje regrutaciju u hromatinu.[23] Mjesto acetilacije AR-a ključna je meta NAD-zavisne i TSA-zavisne histonske deacetilaze i duge nekodirajuće RNK.[24]

Negenomski uredi

Dedavno pokazalo se da androgeni receptori imaju drugi način djelovanja. Kao što je utvrđeno i za druge receptore steroidnih hormona, kao što su estrogeni receptori, androgeni receptori mogu djelovati neovisno o njihovoj interakciji s DNK.[25] Androgeni receptori stupaju u interakciju sa određenim proteinima prenošenja signala u citoplazmi. Vezanje androgena na citoplazmatske androgene receptore može prouzrokovati brze promjene u funkciji ćelija, neovisno o promjenama u transkripciji gena, poput promjena u transportu iona. Regulacija puteva transdukcije signala citoplazmatskim androgenim receptorima može indirektno dovesti do promena u transkripciji gena, naprimjer, dovodeći do fosforilacije drugih faktora transkripcije.

Genetika uredi

Gen uredi

Kod ljudi, androgeni receptor je kodiran AR genom koji se nalazi na X hromosomu na poziciji Xq11-12.[26][27]

Nedostaci uredi

Sindrom neosjetljivosti na androgen, prije poznat kao feminizacija testisa, uzrokovan je mutacijom gena androgenih receptora na X hromosomu (lokus: Xq11 – Xq12). Čini se da androgeni receptor utiče na neuronsku fiziologiju i oštećen je Kenneddyjevom bolešču.[28] Androgeni receptor utiče na fiziologiju neurona i oštećuje ga Kennedyjeva bolest.[29][30] Pored toga, tačkaste mutacije i polimorfizam trinukleotidno ponavljanje povezani su s nizom dodatnih poremećaja.[31]

Ponavljanja C-A-G uredi

AR gen sadrži ponavljanja sekvence C-A-G koja utiču na funkciju receptora, gdje manje ponavljanja dovodi do povećane osjetljivosti receptora na cirkulirajuće androgene, a više ponavljanja dovodi do smanjene osjetljivosti receptora. Studije su pokazale da postoje rasne varijacije u ponavljanjima CAG,[32][33] s tim da Afroamerikanci imaju manje ponavljanja od kavkazoidnih Amerikanaca koji nisu Latinoamerikanci.[32] Rasni trendovi u CAG ponavljanuju imaju paralelu sa incidencijom i smrtnošću od raka prostate u ovim skupinama.

Struktura uredi

 
Strukturni domeni dvije izoforme (AR-A i AR-B) ljudskih androgenih receptora.
Brojevi iznad traka odnose se na aminokiselinske ostatke koji razdvajaju domene, počevši od N-kraja (lijevo) do C-kraja (desno).
NTD = N-terminalni domen, DBD = DNA-vezujući domen, LBD = ligand-vezujući domen, AF = funkcija aktivacije.

Izoforme uredi

Identificirane su dvije izoforme receptora androgena (A i B):[34]

Domeni uredi

Poput ostalih jwedarnih receptora, androgeni receptor je modularne strukture i sastoji se od sljedećih funkcionalnih domena označenih sa A do F:[36]

Također pogledajte uredi

Reference uredi

  1. ^ Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS (juni 1995). "Androgen receptor defects: historical, clinical, and molecular perspectives". Endocrine Reviews. 16 (3): 271–321. doi:10.1210/edrv-16-3-271. PMID 7671849.
  2. ^ Gottlieb B, Lombroso R, Beitel LK, Trifiro MA (januar 2005). "Molecular pathology of the androgen receptor in male (in)fertility". Reproductive Biomedicine Online. 10 (1): 42–8. doi:10.1016/S1472-6483(10)60802-4. PMID 15705293.
  3. ^ Choong CS, Wilson EM (decembar 1998). "Trinucleotide repeats in the human androgen receptor: a molecular basis for disease". Journal of Molecular Endocrinology. 21 (3): 235–57. doi:10.1677/jme.0.0210235. PMID 9845666.
  4. ^ Meehan KL, Sadar MD (maj 2003). "Androgens and androgen receptor in prostate and ovarian malignancies". Frontiers in Bioscience. 8 (1–3): d780–800. doi:10.2741/1063. PMID 12700055.
  5. ^ Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA (decembar 2006). "International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors". Pharmacological Reviews. 58 (4): 782–97. doi:10.1124/pr.58.4.9. PMID 17132855.
  6. ^ Roy AK, Lavrovsky Y, Song CS, Chen S, Jung MH, Velu NK, Bi BY, Chatterjee B (1999). Regulation of androgen action. Vitamins & Hormones. 55. str. 309–52. doi:10.1016/S0083-6729(08)60938-3. ISBN 978-0-12-709855-5. PMID 9949684.
  7. ^ Bardin CW, Brown T, Isomaa VV, Jänne OA (1983). "Progestins can mimic, inhibit and potentiate the actions of androgens". Pharmacology & Therapeutics. 23 (3): 443–59. doi:10.1016/0163-7258(83)90023-2. PMID 6371845.
  8. ^ Raudrant D, Rabe T (2003). "Progestogens with antiandrogenic properties". Drugs. 63 (5): 463–92. doi:10.2165/00003495-200363050-00003. PMID 12600226.
  9. ^ Mooradian AD, Morley JE, Korenman SG (februar 1987). "Biological actions of androgens". Endocrine Reviews. 8 (1): 1–28. doi:10.1210/edrv-8-1-1. PMID 3549275.
  10. ^ Heinlein CA, Chang C (oktobar 2002). "The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions". Molecular Endocrinology. 16 (10): 2181–7. doi:10.1210/me.2002-0070. PMID 12351684.
  11. ^ Davison SL, Bell R (april 2006). "Androgen physiology". Seminars in Reproductive Medicine. 24 (2): 71–7. doi:10.1055/s-2006-939565. PMID 16633980.
  12. ^ Sinisi AA, Pasquali D, Notaro A, Bellastella A (2003). "Sexual differentiation". Journal of Endocrinological Investigation. 26 (3 Suppl): 23–28. PMID 12834017.
  13. ^ Frank GR (septembar 2003). "Role of estrogen and androgen in pubertal skeletal physiology". Medical and Pediatric Oncology. 41 (3): 217–21. doi:10.1002/mpo.10340. PMID 12868122.
  14. ^ Walters KA, Simanainen U, Handelsman DJ (mart 2010). "Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models". Human Reproduction Update. 16 (5): 543–58. doi:10.1093/humupd/dmq003. PMID 20231167.
  15. ^ Sinnesael M, Claessens F, Laurent M, Dubois V, Boonen S, Deboel L, Vanderschueren D (decembar 2012). "Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: evidence from targeted AR disruption in mouse osteocytes". Journal of Bone and Mineral Research. 27 (12): 2535–43. doi:10.1002/jbmr.1713. PMID 22836391.
  16. ^ Heemers HV, Tindall DJ (decembar 2007). "Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex". Endocrine Reviews. 28 (7): 778–808. doi:10.1210/er.2007-0019. PMID 17940184.
  17. ^ Pandini G, Mineo R, Frasca F, Roberts CT, Marcelli M, Vigneri R, Belfiore A (mart 2005). "Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells". Cancer Research. 65 (5): 1849–57. doi:10.1158/0008-5472.CAN-04-1837. PMID 15753383.
  18. ^ Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ (mart 2005). "Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene". The Journal of Biological Chemistry. 280 (9): 7786–92. doi:10.1074/jbc.M413992200. PMID 15623502.
  19. ^ Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, Ogryzko V, Avantaggiati ML, Pestell RG (juli 2000). "p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation". The Journal of Biological Chemistry. 275 (27): 20853–60. doi:10.1074/jbc.M000660200. PMID 10779504.
  20. ^ Fu M, Wang C, Wang J, Zhang X, Sakamaki T, Yeung YG, Chang C, Hopp T, Fuqua SA, Jaffray E, Hay RT, Palvimo JJ, Jänne OA, Pestell RG (maj 2002). "Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function". Molecular and Cellular Biology. 22 (10): 3373–88. doi:10.1128/mcb.22.10.3373-3388.2002. PMC 133781. PMID 11971970.
  21. ^ Fu M, Rao M, Wang C, Sakamaki T, Wang J, Di Vizio D, Zhang X, Albanese C, Balk S, Chang C, Fan S, Rosen E, Palvimo JJ, Jänne OA, Muratoglu S, Avantaggiati ML, Pestell RG (decembar 2003). "Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth". Molecular and Cellular Biology. 23 (23): 8563–75. doi:10.1128/mcb.23.23.8563-8575.2003. PMC 262657. PMID 14612401.
  22. ^ Gong J, Zhu J, Goodman OB, Pestell RG, Schlegel PN, Nanus DM, Shen R (mart 2006). "Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells". Oncogene. 25 (14): 2011–21. doi:10.1038/sj.onc.1209231. PMID 16434977.
  23. ^ Fu M, Rao M, Wu K, Wang C, Zhang X, Hessien M, Yeung YG, Gioeli D, Weber MJ, Pestell RG (juli 2004). "The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity". The Journal of Biological Chemistry. 279 (28): 29436–49. doi:10.1074/jbc.M313466200. PMID 15123687.
  24. ^ Yang L, Lin C, Jin C, Yang JC, Tanasa B, Li W, Merkurjev D, Ohgi KA, Meng D, Zhang J, Evans CP, Rosenfeld MG (august 2013). "lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs". Nature. 500 (7464): 598–602. doi:10.1038/nature12451. PMC 4034386. PMID 23945587.
  25. ^ Fix C, Jordan C, Cano P, Walker WH (juli 2004). "Testosterone activates mitogen-activated protein kinase and the cAMP response element binding protein transcription factor in Sertoli cells". Proceedings of the National Academy of Sciences of the United States of America. 101 (30): 10919–24. doi:10.1073/pnas.0404278101. PMC 503720. PMID 15263086.
  26. ^ Chang CS, Kokontis J, Liao ST (april 1988). "Molecular cloning of human and rat complementary DNA encoding androgen receptors". Science. 240 (4850): 324–6. doi:10.1126/science.3353726. PMID 3353726.
  27. ^ Trapman J, Klaassen P, Kuiper GG, van der Korput JA, Faber PW, van Rooij HC, Geurts van Kessel A, Voorhorst MM, Mulder E, Brinkmann AO (maj 1988). "Cloning, structure and expression of a cDNA encoding the human androgen receptor". Biochemical and Biophysical Research Communications. 153 (1): 241–8. doi:10.1016/S0006-291X(88)81214-2. PMID 3377788.
  28. ^ Brown TR (1995). "Human androgen insensitivity syndrome". Journal of Andrology. 16 (4): 299–303. PMID 8537246. Arhivirano s originala (abstract), 24. 7. 2008.
  29. ^ Kennedy WR, Alter M, Sung JH (juli 1968). "Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait". Neurology. 18 (7): 671–80. doi:10.1212/WNL.18.7.671. PMID 4233749.
  30. ^ Yu Z, Dadgar N, Albertelli M, Gruis K, Jordan C, Robins DM, Lieberman AP (oktobar 2006). "Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model". The Journal of Clinical Investigation. 116 (10): 2663–72. doi:10.1172/JCI28773. PMC 1564432. PMID 16981011.
  31. ^ Rajender S, Singh L, Thangaraj K (mart 2007). "Phenotypic heterogeneity of mutations in androgen receptor gene". Asian Journal of Andrology. 9 (2): 147–79. doi:10.1111/j.1745-7262.2007.00250.x. PMID 17334586.
  32. ^ a b Sartor O, Zheng Q, Eastham JA (februar 1999). "Androgen receptor gene CAG repeat length varies in a race-specific fashion in men without prostate cancer". Urology. 53 (2): 378–80. doi:10.1016/s0090-4295(98)00481-6. PMID 9933058.
  33. ^ Weintrob N, Eyal O, Slakman M, Segev Becker A, Israeli G, Kalter-Leibovici O, Ben-Shachar S (2018). "The effect of CAG repeats length on differences in hirsutism among healthy Israeli women of different ethnicities". PLOS ONE. 13 (3): e0195046. doi:10.1371/journal.pone.0195046. PMC 5871002. PMID 29584789.
  34. ^ Wilson CM, McPhaul MJ (februar 1994). "A and B forms of the androgen receptor are present in human genital skin fibroblasts". Proceedings of the National Academy of Sciences of the United States of America. 91 (4): 1234–8. doi:10.1073/pnas.91.4.1234. PMC 43131. PMID 8108393.
  35. ^ Gregory CW, He B, Wilson EM (decembar 2001). "The putative androgen receptor-A form results from in vitro proteolysis". Journal of Molecular Endocrinology. 27 (3): 309–19. doi:10.1677/jme.0.0270309. PMID 11719283.
  36. ^ Brinkmann AO, Klaasen P, Kuiper GG, van der Korput JA, Bolt J, de Boer W, Smit A, Faber PW, van Rooij HC, Geurts van Kessel A (1989). "Structure and function of the androgen receptor". Urological Research. 17 (2): 87–93. doi:10.1007/BF00262026. PMID 2734982.
  37. ^ Jenster G, van der Korput HA, Trapman J, Brinkmann AO (mart 1995). "Identification of two transcription activation units in the N-terminal domain of the human androgen receptor" (PDF). The Journal of Biological Chemistry. 270 (13): 7341–6. doi:10.1074/jbc.270.13.7341. PMID 7706276.
  38. ^ Schaufele F, Carbonell X, Guerbadot M, Borngraeber S, Chapman MS, Ma AA, Miner JN, Diamond MI (juli 2005). "The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions". Proceedings of the National Academy of Sciences of the United States of America. 102 (28): 9802–7. doi:10.1073/pnas.0408819102. PMC 1168953. PMID 15994236.
  39. ^ Klokk TI, Kurys P, Elbi C, Nagaich AK, Hendarwanto A, Slagsvold T, Chang CY, Hager GL, Saatcioglu F (mart 2007). "Ligand-specific dynamics of the androgen receptor at its response element in living cells". Molecular and Cellular Biology. 27 (5): 1823–43. doi:10.1128/MCB.01297-06. PMC 1820481. PMID 17189428.
  40. ^ van Royen ME, Cunha SM, Brink MC, Mattern KA, Nigg AL, Dubbink HJ, Verschure PJ, Trapman J, Houtsmuller AB (april 2007). "Compartmentalization of androgen receptor protein-protein interactions in living cells". The Journal of Cell Biology. 177 (1): 63–72. doi:10.1083/jcb.200609178. PMC 2064112. PMID 17420290.
  41. ^ Langley E, Zhou ZX, Wilson EM (decembar 1995). "Evidence for an anti-parallel orientation of the ligand-activated human androgen receptor dimer". The Journal of Biological Chemistry. 270 (50): 29983–90. doi:10.1074/jbc.270.50.29983. PMID 8530400.
  42. ^ Berrevoets CA, Doesburg P, Steketee K, Trapman J, Brinkmann AO (august 1998). "Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2)". Molecular Endocrinology. 12 (8): 1172–83. doi:10.1210/me.12.8.1172. PMID 9717843.
  43. ^ a b Dubbink HJ, Hersmus R, Verma CS, van der Korput HA, Berrevoets CA, van Tol J, Ziel-van der Made AC, Brinkmann AO, Pike AC, Trapman J (septembar 2004). "Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor". Molecular Endocrinology. 18 (9): 2132–50. doi:10.1210/me.2003-0375. PMID 15178743.
  44. ^ Kaku N, Matsuda K, Tsujimura A, Kawata M (august 2008). "Characterization of nuclear import of the domain-specific androgen receptor in association with the importin alpha/beta and Ran-guanosine 5'-triphosphate systems". Endocrinology. 149 (8): 3960–9. doi:10.1210/en.2008-0137. PMC 2488236. PMID 18420738.
  45. ^ Saporita AJ, Zhang Q, Navai N, Dincer Z, Hahn J, Cai X, Wang Z (oktobar 2003). "Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor". The Journal of Biological Chemistry. 278 (43): 41998–2005. doi:10.1074/jbc.M302460200. PMID 12923188.
  46. ^ Wang L, Hsu CL, Ni J, Wang PH, Yeh S, Keng P, Chang C (mart 2004). "Human checkpoint protein hRad9 functions as a negative coregulator to repress androgen receptor transactivation in prostate cancer cells". Molecular and Cellular Biology. 24 (5): 2202–13. doi:10.1128/MCB.24.5.2202-2213.2004. PMC 350564. PMID 14966297.
  47. ^ Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC, Rennie PS (decembar 2002). "RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor". The Journal of Biological Chemistry. 277 (50): 48020–7. doi:10.1074/jbc.M209741200. PMID 12361945.
  48. ^ Beitel LK, Elhaji YA, Lumbroso R, Wing SS, Panet-Raymond V, Gottlieb B, Pinsky L, Trifiro MA (august 2002). "Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity". Journal of Molecular Endocrinology. 29 (1): 41–60. doi:10.1677/jme.0.0290041. PMID 12200228.
  49. ^ Lu J, Danielsen M (novembar 1998). "Differential regulation of androgen and glucocorticoid receptors by retinoblastoma protein". The Journal of Biological Chemistry. 273 (47): 31528–33. doi:10.1074/jbc.273.47.31528. PMID 9813067.
  50. ^ Yeh S, Miyamoto H, Nishimura K, Kang H, Ludlow J, Hsiao P, Wang C, Su C, Chang C (juli 1998). "Retinoblastoma, a tumor suppressor, is a coactivator for the androgen receptor in human prostate cancer DU145 cells". Biochemical and Biophysical Research Communications. 248 (2): 361–7. doi:10.1006/bbrc.1998.8974. PMID 9675141.
  51. ^ Miyamoto H, Rahman M, Takatera H, Kang HY, Yeh S, Chang HC, Nishimura K, Fujimoto N, Chang C (februar 2002). "A dominant-negative mutant of androgen receptor coregulator ARA54 inhibits androgen receptor-mediated prostate cancer growth". The Journal of Biological Chemistry. 277 (7): 4609–17. doi:10.1074/jbc.M108312200. PMID 11673464.
  52. ^ Kang HY, Yeh S, Fujimoto N, Chang C (mart 1999). "Cloning and characterization of human prostate coactivator ARA54, a novel protein that associates with the androgen receptor". The Journal of Biological Chemistry. 274 (13): 8570–6. doi:10.1074/jbc.274.13.8570. PMID 10085091.
  53. ^ Moilanen AM, Poukka H, Karvonen U, Häkli M, Jänne OA, Palvimo JJ (septembar 1998). "Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene transcription". Molecular and Cellular Biology. 18 (9): 5128–39. doi:10.1128/mcb.18.9.5128. PMC 109098. PMID 9710597.
  54. ^ Poukka H, Aarnisalo P, Santti H, Jänne OA, Palvimo JJ (januar 2000). "Coregulator small nuclear RING finger protein (SNURF) enhances Sp1- and steroid receptor-mediated transcription by different mechanisms". The Journal of Biological Chemistry. 275 (1): 571–9. doi:10.1074/jbc.275.1.571. PMID 10617653.
  55. ^ Liu Y, Kim BO, Kao C, Jung C, Dalton JT, He JJ (maj 2004). "Tip110, the human immunodeficiency virus type 1 (HIV-1) Tat-interacting protein of 110 kDa as a negative regulator of androgen receptor (AR) transcriptional activation". The Journal of Biological Chemistry. 279 (21): 21766–73. doi:10.1074/jbc.M314321200. PMID 15031286.
  56. ^ Fu M, Liu M, Sauve AA, Jiao X, Zhang X, Wu X, Powell MJ, Yang T, Gu W, Avantaggiati ML, Pattabiraman N, Pestell TG, Wang F, Quong AA, Wang C, Pestell RG (novembar 2006). "Hormonal control of androgen receptor function through SIRT1". Molecular and Cellular Biology. 26 (21): 8122–35. doi:10.1128/MCB.00289-06. PMC 1636736. PMID 16923962.
  57. ^ Chipuk JE, Cornelius SC, Pultz NJ, Jorgensen JS, Bonham MJ, Kim SJ, Danielpour D (januar 2002). "The androgen receptor represses transforming growth factor-beta signaling through interaction with Smad3". The Journal of Biological Chemistry. 277 (2): 1240–8. doi:10.1074/jbc.M108855200. PMID 11707452.
  58. ^ Hayes SA, Zarnegar M, Sharma M, Yang F, Peehl DM, ten Dijke P, Sun Z (mart 2001). "SMAD3 represses androgen receptor-mediated transcription". Cancer Research. 61 (5): 2112–8. PMID 11280774.
  59. ^ Kang HY, Huang KE, Chang SY, Ma WL, Lin WJ, Chang C (novembar 2002). "Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4". The Journal of Biological Chemistry. 277 (46): 43749–56. doi:10.1074/jbc.M205603200. PMID 12226080.
  60. ^ Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (decembar 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry. 40 (50): 15369–77. doi:10.1021/bi011384o. PMID 11735420.
  61. ^ Unni E, Sun S, Nan B, McPhaul MJ, Cheskis B, Mancini MA, Marcelli M (oktobar 2004). "Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence". Cancer Research. 64 (19): 7156–68. doi:10.1158/0008-5472.CAN-04-1121. PMID 15466214.
  62. ^ Powell SM, Christiaens V, Voulgaraki D, Waxman J, Claessens F, Bevan CL (mart 2004). "Mechanisms of androgen receptor signalling via steroid receptor coactivator-1 in prostate". Endocrine-Related Cancer. 11 (1): 117–30. doi:10.1677/erc.0.0110117. PMID 15027889.
  63. ^ Yuan X, Lu ML, Li T, Balk SP (decembar 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". The Journal of Biological Chemistry. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838.
  64. ^ Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A (april 2001). "Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells". Biochemical and Biophysical Research Communications. 283 (1): 179–87. doi:10.1006/bbrc.2001.4758. PMID 11322786.
  65. ^ Ueda T, Bruchovsky N, Sadar MD (mart 2002). "Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways". The Journal of Biological Chemistry. 277 (9): 7076–85. doi:10.1074/jbc.M108255200. PMID 11751884.
  66. ^ Ting HJ, Yeh S, Nishimura K, Chang C (januar 2002). "Supervillin associates with androgen receptor and modulates its transcriptional activity". Proceedings of the National Academy of Sciences of the United States of America. 99 (2): 661–6. doi:10.1073/pnas.022469899. PMC 117362. PMID 11792840.
  67. ^ Mu X, Chang C (oktobar 2003). "TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3". The Prostate. 57 (2): 129–33. doi:10.1002/pros.10282. PMID 12949936.
  68. ^ Lee YF, Shyr CR, Thin TH, Lin WJ, Chang C (decembar 1999). "Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily". Proceedings of the National Academy of Sciences of the United States of America. 96 (26): 14724–9. doi:10.1073/pnas.96.26.14724. PMC 24715. PMID 10611280.
  69. ^ He B, Minges JT, Lee LW, Wilson EM (mart 2002). "The FXXLF motif mediates androgen receptor-specific interactions with coregulators". The Journal of Biological Chemistry. 277 (12): 10226–35. doi:10.1074/jbc.M111975200. PMID 11779876.
  70. ^ Wang X, Yang Y, Guo X, Sampson ER, Hsu CL, Tsai MY, Yeh S, Wu G, Guo Y, Chang C (maj 2002). "Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator". The Journal of Biological Chemistry. 277 (18): 15426–31. doi:10.1074/jbc.M111218200. PMID 11856738.
  71. ^ Hsiao PW, Chang C (august 1999). "Isolation and characterization of ARA160 as the first androgen receptor N-terminal-associated coactivator in human prostate cells". The Journal of Biological Chemistry. 274 (32): 22373–9. doi:10.1074/jbc.274.32.22373. PMID 10428808.
  72. ^ Miyajima N, Maruyama S, Bohgaki M, Kano S, Shigemura M, Shinohara N, Nonomura K, Hatakeyama S (maj 2008). "TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells". Cancer Research. 68 (9): 3486–94. doi:10.1158/0008-5472.CAN-07-6059. PMID 18451177.
  73. ^ Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP (oktobar 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Molecular Endocrinology. 18 (10): 2388–401. doi:10.1210/me.2003-0436. PMID 15256534.
  74. ^ Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Jänne OA (juli 1999). "Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription". The Journal of Biological Chemistry. 274 (27): 19441–6. doi:10.1074/jbc.274.27.19441. PMID 10383460.
  75. ^ Müller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schüle R (februar 2000). "FHL2, a novel tissue-specific coactivator of the androgen receptor". The EMBO Journal. 19 (3): 359–69. doi:10.1093/emboj/19.3.359. PMC 305573. PMID 10654935.
  76. ^ Cheng S, Brzostek S, Lee SR, Hollenberg AN, Balk SP (juli 2002). "Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor". Molecular Endocrinology. 16 (7): 1492–501. doi:10.1210/mend.16.7.0870. PMID 12089345.
  77. ^ Hodgson MC, Astapova I, Cheng S, Lee LJ, Verhoeven MC, Choi E, Balk SP, Hollenberg AN (februar 2005). "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". The Journal of Biological Chemistry. 280 (8): 6511–9. doi:10.1074/jbc.M408972200. PMID 15598662.
  78. ^ Markus SM, Taneja SS, Logan SK, Li W, Ha S, Hittelman AB, Rogatsky I, Garabedian MJ (februar 2002). "Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus". Molecular Biology of the Cell. 13 (2): 670–82. doi:10.1091/mbc.01-10-0513. PMC 65658. PMID 11854421.
  79. ^ Sharma M, Li X, Wang Y, Zarnegar M, Huang CY, Palvimo JJ, Lim B, Sun Z (novembar 2003). "hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci". The EMBO Journal. 22 (22): 6101–14. doi:10.1093/emboj/cdg585. PMC 275443. PMID 14609956.

Vanjski linkovi uredi

Šablon:Transcripcijski faktori