OGFr
Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a protein which in humans is encoded by the OGFR gene.[5][6] The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. The endogenous ligand is thus a known opioid peptide, and OGFr was originally discovered and named as a new opioid receptor zeta (ζ). However it was subsequently found that it shares little sequence similarity with the other opioid receptors, and has quite different function.
| OGFR | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | OGFR, OGFr, opioid growth factor receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 606459 MGI: 1919325 HomoloGene: 7199 GeneCards: OGFR | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Opioid growth factor receptor (OGFr) conserved region | |||||||||
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| Identifiers | |||||||||
| Symbol | OGFr_N | ||||||||
| Pfam | PF04664 | ||||||||
| InterPro | IPR006757 | ||||||||
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| Opioid growth factor receptor repeat | |||||||||
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| Identifiers | |||||||||
| Symbol | OGFr_III | ||||||||
| Pfam | PF04680 | ||||||||
| InterPro | IPR006770 | ||||||||
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Function
The natural function of this receptor appears to be in regulation of tissue growth,[7][8][9][10] and it has been shown to be important in embryonic development,[11] wound repair,[12] and certain forms of cancer.[13][14][15][16]
OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported.[5]
Mechanism of activation
The opioid growth factor receptor consists of a chain of 677 amino acids, which includes a nuclear localization sequence region. When OGF binds to the receptor, an OGF-OGFr complex is formed, which leads to the increase in the synthesis of the selective cyclin-dependent kinase (CDK) inhibitor proteins, p12 and p16. Retinoblastoma protein becomes inactivated through phosphorylation by CDKs, and leads to the progression of the cell cycle from the G1 phase to the S phase. Because the activation of the OGF receptor, blocks the phosphorylation of retinoblastoma proteins, retardation of the G1 phase occurs, which prevents the cell from further dividing.[17][18]
Therapeutic applications
Upregulation of OGFr and consequent stimulation of the OGF-OGFr system are important for the anti-proliferative effects of imidazoquinoline drugs like imiquimod and resiquimod, which are immune response modifiers with potent antiviral and antitumour effects, used as topical creams for the treatment of skin cancers and warts.[19]
Structure
OGF contains a conserved N-terminal domain followed by a series of imperfect repeats.[8]
References
- GRCh38: Ensembl release 89: ENSG00000060491 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000049401 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: OGFR opioid growth factor receptor".
- Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (February 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. PMID 10677613. S2CID 37516655.
- 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. PMID 9566952.
- Zagon IS, Verderame MF, McLaughlin PJ (February 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. PMID 11890982. S2CID 37812525.
- 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. doi:10.3892/ijmm.15.5.841. PMID 15806307.
- Cheng F, McLaughlin PJ, Verderame MF, Zagon IS (January 2009). "The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation". Molecular Biology of the Cell. 20 (1): 319–27. doi:10.1091/mbc.E08-07-0681. PMC 2613082. PMID 18923142.
- Zagon IS, Wu Y, McLaughlin PJ (August 1999). "Opioid growth factor and organ development in rat and human embryos". Brain Res. 839 (2): 313–22. doi:10.1016/S0006-8993(99)01753-9. PMID 10519055. S2CID 22000619.
- 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. PMID 12854052. S2CID 34449136.
- 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. doi:10.3892/ijo.14.3.577. PMID 10024694.
- 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. doi:10.3892/ijo.14.5.991. PMID 10200353.
- 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 Research. 67 (21): 10511–8. doi:10.1158/0008-5472.CAN-07-1922. PMID 17974995.
- 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 Physiology. 296 (6): R1716–25. doi:10.1152/ajpregu.00075.2009. PMID 19297547.
- Zagon IS, Donahue RN, McLaughlin PJ (2009). "Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 297 (4): R1154–61. doi:10.1152/ajpregu.00414.2009. PMID 19675283.
- Avella DM, Kimchi ET, Donahue RN, Tagaram HR, McLaughlin PJ, Zagon IS, Staveley-O'Carroll KF (2010). "The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 298 (2): R459–66. doi:10.1152/ajpregu.00646.2009. PMC 2828179. PMID 19923357.
- 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. 233 (8): 968–79. doi:10.3181/0802-RM-58. PMID 18480416. S2CID 35164284.
Further reading
- 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. PMID 11890982. S2CID 37812525.
- 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. PMID 10677613. S2CID 37516655.
- Wu CJ, Yang XF, McLaughlin S, et al. (2000). "Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia". J. Clin. Invest. 106 (5): 705–14. doi:10.1172/JCI10196. PMC 381287. PMID 10974024.
- 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. PMID 11214971.
- Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- 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. PMID 12650964. S2CID 30270018.
- 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. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- 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. doi:10.3892/ijo.28.6.1577. PMID 16685459.
- 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. doi:10.3892/ijo.29.2.489. PMID 16820893.
- Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
- 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. doi:10.3892/ijmm.19.3.421. PMID 17273790.