Receptor vitamina D

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Receptor vitamina D
PDB 2hb8 EBI.jpg
Vitamin D (1,25- dihidroksivitamin D3) receptor
(427 aminokiselina)
Identifikatori
Symbol

VDR

Name = Receptor vitamina D
InterPro 12679
SCOP vezanje sa vitaminom D; Heterodimer VDR+RXRA Homodimer; vezanje sa vitaminom D; Heterodimer VDR+RXRA
SUPERFAMILY vezanje sa vitaminom D; Heterodimer VDR+RXRA Homodimer; vezanje sa vitaminom D; Heterodimer VDR+RXRA
OPM superfamily [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1YY1 1YY1, ABCD 1YY1, ABCD]

Receptor kalcitriola – poznat i kao receptor vitamina D (VDR) i NR1 I 1 (potporodica nuklearnih receptora 1, grupa I, član 1) – je član porodice nuklearnih receptora transkripcijskih faktora.[1] Nakon aktivacije vitamina D, VDR formira heterodimer sa retinoidnim X receptorom i veže sa elementima hormonskog odgovora na DNK. To rezultira u ispoljavanju ili transrepresiji specifičnih genskih proizvoda. VDR-i ne reguliraju samo transkripcijski odgovor, već su uključeni i u posttranskripcijske mehanizme koje usmjerava mikroRNK.[2] Kod ljudi, receptor vitamina D je kodiran genom VDR.[3]

Glukokortikoidi su poznati po smanjivanju ekspresije VDR, što se ispoljava u većini tkiva, a u probavnom traktu regulira transport kalcija, željeza i ostalih minerala.[4]

Funkcija[uredi | uredi izvor]

Sinteza receptora vitamina vitamina D3 je genetički kontrolrana. Ovaj receptor istovremeno funkcionira i kao sekundarna žučna i lithoholna kiselina. Receptor pripada porodici of trans-activnih transcripcijskih regulatornih factora i pokazuju sličnost sekvence sa receptorima steroidnih i tiroidnih hormona.[5]

Nizvodni ciljevi ovog nuklearnog receptora hormona su uključeni uglavnom u metabolizam minerala, iako receptor regulira i niz drugih metaboličkih puteva, kao što su oni koji su uključeni u imuni odgovor i rak.[6]

Mutacije u ovom genu su povezane sa rezistentnošću rahitisa na vitamin D, tip II. Jednostruki nuklearni polimorfizam u inicijacijskom kodonu rezultira izmijenjenom translacijom startnog mjesta, tri kodona nizvodno. Alternativna prerada RNK se ispoljava u više transkribiranih varijanti koje kodiraju isti protein.[7]

Receptor vitamina D ima važnu ulogu u reguliranju ciklusa rasta dlake. Gubitak gena VDR je, kod ekperimentalnih životinja, povezan sa gubitkom dlake[8] |slušnog ježaExperimentalna proučavanja pokazuju da neligandirani VDR stupa u interakciju sa ragulacijskom ciljnom regijom gena cWnt (wnt signalni put) i slušnog ježa i pokreće ovaj put tokom postnatalnog ciklusa rasta dlake.[9] Ove studije su otkrile nove akcije neligandskih VDR u reguliranju post-morfogenog ciklusa dlake.

Interakcije[uredi | uredi izvor]

Kalcitriolski receptor pokazuje interakcije protein-proteinrotein-protein sa

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

  1. ^ Moore DD, Kato S, Xie W, Mangelsdorf DJ, Schmidt DR, Xiao R, Kliewer SA (December 2006). "International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor". Pharmacol. Rev. 58 (4): 742–59. PMID 17132852. doi:10.1124/pr.58.4.6. 
  2. ^ Lisse TS, Chun RF, Rieger S, Adams JS, Hewison M (June 2013). "Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts". J Bone Miner Res. 28 (6): 1478–14788. PMID 23362149. doi:10.1002/jbmr.1882. 
  3. ^ Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, Wiese R, DeLuca HF (September 1991). "The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D3 receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7". Genomics 11 (1): 168–73. PMID 1662663. doi:10.1016/0888-7543(91)90114-T. 
  4. ^ Fleet JC, Schoch RD (August 2010). "Molecular Mechanisms for Regulation of Intestinal Calcium Absorption by Vitamin D and Other Factors". Crit Rev Clin Lab Sci 47 (4): 181–195. PMID 21182397. doi:10.3109/10408363.2010.536429. 
  5. ^ Germain P, Staels B, Dacquet C, Spedding M, Laudet V (December 2006). "Overview of nomenclature of nuclear receptors". Pharmacol. Rev. 58 (4): 685–704. PMID 17132848. doi:10.1124/pr.58.4.2. 
  6. ^ Adorini L, Daniel KC, Penna G (2006). "Vitamin D receptor agonists, cancer and the immune system: an intricate relationship". Curr Top Med Chem 6 (12): 1297–301. PMID 16848743. doi:10.2174/156802606777864890. 
  7. ^ "Entrez Gene: VDR vitamin D (1,25- dihydroxyvitamin D3) receptor". 
  8. ^ Luderer HF, Demay MB (July 2010). "The vitamin D receptor, the skin and stem cells". J. Steroid Biochem. Mol. Biol. 121 (1–2): 314–6. PMID 20138991. doi:10.1016/j.jsbmb.2010.01.015. 
  9. ^ Lisse TS, Saini V, Zhao H, Luderer HF, Gori F, Demay MB (September 2014). "The Vitamin D Receptor Is Required for Activation of cWnt and Hedgehog Signaling in Keratinocytes". Mol. Endocrinol. 28 (10): 1698–1706. PMID 25180455. doi:10.1210/me.2014-1043. 
  10. ^ Guzey M, Takayama S, Reed JC (December 2000). "BAG1L enhances trans-activation function of the vitamin D receptor". J. Biol. Chem. 275 (52): 40749–56. PMID 10967105. doi:10.1074/jbc.M004977200. 
  11. ^ a b c d e Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (June 2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell 113 (7): 905–17. PMID 12837248. doi:10.1016/S0092-8674(03)00436-7. 
  12. ^ Zhao G, Simpson RU (2010). "Membrane Localization, Caveolin-3 Association and Rapid Actions of Vitamin D Receptor in Cardiac Myocytes". Steroids 75 (8–9): 555–9. PMC 2885558. PMID 20015453. doi:10.1016/j.steroids.2009.12.001. 
  13. ^ a b Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (March 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Mol. Cell 3 (3): 361–70. PMID 10198638. doi:10.1016/S1097-2765(00)80463-3. 
  14. ^ a b Tagami T, Lutz WH, Kumar R, Jameson JL (December 1998). "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochem. Biophys. Res. Commun. 253 (2): 358–63. PMID 9878542. doi:10.1006/bbrc.1998.9799. 
  15. ^ a b c d Puccetti E, Obradovic D, Beissert T, Bianchini A, Washburn B, Chiaradonna F, Boehrer S, Hoelzer D, Ottmann OG, Pelicci PG, Nervi C, Ruthardt M (December 2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Res. 62 (23): 7050–8. PMID 12460926. 
  16. ^ Herdick M, Steinmeyer A, Carlberg C (June 2000). "Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators". J. Biol. Chem. 275 (22): 16506–12. PMID 10748178. doi:10.1074/jbc.M910000199. 
  17. ^ a b c Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN (November 2001). "Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription". J. Biol. Chem. 276 (44): 40614–20. PMID 11514567. doi:10.1074/jbc.M106263200. 
  18. ^ He B, Wilson EM (March 2003). "Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs". Mol. Cell. Biol. 23 (6): 2135–50. PMC 149467. PMID 12612084. doi:10.1128/MCB.23.6.2135-2150.2003. 
  19. ^ a b Baudino TA, Kraichely DM, Jefcoat SC, Winchester SK, Partridge NC, MacDonald PN (June 1998). "Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription". J. Biol. Chem. 273 (26): 16434–41. PMID 9632709. doi:10.1074/jbc.273.26.16434. 
  20. ^ Vidal M, Ramana CV, Dusso AS (April 2002). "Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription". Mol. Cell. Biol. 22 (8): 2777–87. PMC 133712. PMID 11909970. doi:10.1128/MCB.22.8.2777-2787.2002. 
  21. ^ Ward JO, McConnell MJ, Carlile GW, Pandolfi PP, Licht JD, Freedman LP (December 2001). "The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D(3)-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D(3) receptor". Blood 98 (12): 3290–300. PMID 11719366. doi:10.1182/blood.V98.12.3290. 

Vanjski linkovi[uredi | uredi izvor]