Receptor opioidnog faktora rasta, OGFr ili ζ-opioidni receptor, je protein koji je kod čoveka kodiran OGFRgenom.[1][2] On je receptor opioidnog faktora rasta (OGF), takođe poznatog kao Met-enkefalin. To je endogeni ligand ovog receptora. OGFr je originalno bio otkriven i nazvan kao novi opioidni receptor zeta (ζ). Međutim naknadno je utvrđeno da on ima neznatnu homologiju sekvence sa drugim opioidnim receptorima, i da ima veoma različitu funkciju.
Funkcija
Prirodna funkcija ovog receptora je regulacija rasta tkiva,[3][4][5][6] i bilo je pokazano da je važan u embrionskom razvoju,[7] zarastanju rana,[8] i za pojedine tipove raka.[9][10][11][12]
OGF je negativni regulator ćelijske proliferacije i organizacije tkiva u nizu procesa. Utvrđeno je da je nevezani receptor lokalizovan na spoljašnjosti jedra, gde on vezuje OGF i naknadno biva translociran u jedro. Kodirajuća sekvenca ovog gena sadrži polimorfni region sa 60 nukleotidnim tandemom nesavršenih ponavljajućih jedinica. Iranskripti koji sadrže između nula i osam ponavljajućih jedinica su nađeni.[1]
Terapeutske primena
Povišeno izražavanje OGFr-a i konsekventna stimulacija OGF-OGFr sistema su važni za antiproliferativne efekte imidazohinolinskih lekova kao što su imikuimod i rezikuimod, koji su modifikatori imunskog sistema sa potentnim antivirusnim i antitumorskim dejstvom. Oni se koriste kao topikalni kremovi za lečenje raka kože i bradavica.[13]
↑Wu Y, McLaughlin PJ, Zagon IS (April 1998). „Ontogeny of the opioid growth factor, Met5-enkephalin, preproenkephalin gene expression, and the zeta opioid receptor in the developing and adult aorta of rat”. Dev. Dyn.211 (4): 327–37. DOI:10.1002/(SICI)1097-0177(199804)211:4<327::AID-AJA4>3.0.CO;2-J. PMID9566952.
↑Malendowicz LK, Rebuffat P, Tortorella C, Nussdorfer GG, Ziolkowska A, Hochol A (May 2005). „Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth”. Int. J. Mol. Med.15 (5): 841–5. PMID15806307.
↑Sassani JW, Zagon IS, McLaughlin PJ (May 2003). „Opioid growth factor modulation of corneal epithelium: uppers and downers”. Curr. Eye Res.26 (5): 249–62. DOI:10.1076/ceyr.26.4.249.15427. PMID12854052.
↑Zagon IS, Smith JP, McLaughlin PJ (March 1999). „Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor”. Int. J. Oncol.14 (3): 577–84. PMID10024694.
↑McLaughlin PJ, Levin RJ, Zagon IS (May 1999). „Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor”. Int. J. Oncol.14 (5): 991–8. PMID10200353.
↑Cheng F, Zagon IS, Verderame MF, McLaughlin PJ (November 2007). „The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer”. Cancer Research67 (21): 10511–8. DOI:10.1158/0008-5472.CAN-07-1922. PMID17974995.
↑Donahue RN, McLaughlin PJ, Zagon IS (March 2009). „Cell Proliferation of Human Ovarian Cancer is Regulated by the Opioid Growth Factor - Opioid Growth Factor Receptor Axis”. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology296 (6): R1716–25. DOI:10.1152/ajpregu.00075.2009. PMID19297547.
↑Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ (August 2008). „Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function”. Experimental Biology and Medicine (Maywood, N.J.)233 (8): 968–79. DOI:10.3181/0802-RM-58. PMID18480416.
Literatura
Zagon IS, Verderame MF, McLaughlin PJ (2002). „The biology of the opioid growth factor receptor (OGFr).”. Brain Res. Brain Res. Rev.38 (3): 351–76. DOI:10.1016/S0165-0173(01)00160-6. PMID11890982.
Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (2000). „Cloning, sequencing, chromosomal location, and function of cDNAs encoding an opioid growth factor receptor (OGFr) in humans.”. Brain Res.856 (1-2): 75–83. DOI:10.1016/S0006-8993(99)02330-6. PMID10677613.
Hattori A, Okumura K, Nagase T, et al. (2001). „Characterization of long cDNA clones from human adult spleen.”. DNA Res.7 (6): 357–66. DOI:10.1093/dnares/7.6.357. PMID11214971.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). „The DNA sequence and comparative analysis of human chromosome 20.”. Nature414 (6866): 865–71. DOI:10.1038/414865a. PMID11780052.
Zagon IS, Ruth TB, Leure-duPree AE, et al. (2003). „Immunoelectron microscopic localization of the opioid growth factor receptor (OGFr) and OGF in the cornea.”. Brain Res.967 (1-2): 37–47. DOI:10.1016/S0006-8993(02)04172-0. PMID12650964.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). „Complete sequencing and characterization of 21,243 full-length human cDNAs.”. Nat. Genet.36 (1): 40–5. DOI:10.1038/ng1285. PMID14702039.
McLaughlin PJ, Zagon IS (2006). „Progression of squamous cell carcinoma of the head and neck is associated with down-regulation of the opioid growth factor receptor.”. Int. J. Oncol.28 (6): 1577–83. PMID16685459.
Zagon IS, McLaughlin PJ (2006). „Opioid growth factor receptor is unaltered with the progression of human pancreatic and colon cancers.”. Int. J. Oncol.29 (2): 489–94. PMID16820893.
Olsen JV, Blagoev B, Gnad F, et al. (2006). „Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”. Cell127 (3): 635–48. DOI:10.1016/j.cell.2006.09.026. PMID17081983.
McLaughlin PJ, Verderame MF, Hankins JL, Zagon IS (2007). „Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck.”. Int. J. Mol. Med.19 (3): 421–8. PMID17273790.
