PMEL (gene)
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| Aliases | PMEL, D12S53E, ME20, ME20-M, ME20M, P1, P100, PMEL17, SI, SIL, SILV, gp100, premelanosome protein, HMB-45, HMB45 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 155550; MGI: 98301; GeneCards: PMEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
Structure
MEL is a type I transmembrane glycoprotein that is expressed primarily in melanosomes, which are the melanin-producing organelles in melanocytes of pigment cells of the skin and eye, and in most malignant melanomas. It is 661 amino acids long, with a mass of 100 kDa.
The transmembrane form of PMEL is modified in the secretory pathway by elaboration of N-linked oligosaccharides and addition and modification of O-linked oligosaccharides. It is then targeted to precursors of the pigment organelle, the melanosome, where it is proteolytically processed to several small fragments.
Some of these fragments form non-pathological amyloid that assemble into sheets and form the striated pattern that underlies melanosomal ultrastructure. PMEL cleavage is mediated by several proteases including a proprotein convertase of the furin family, a "sheddase" that might include members of the a disintegrin and metalloproteinase (ADAM) family, and additional proteases in melanosomes or their precursors. After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is digested by γ-secretase.
Function
This protein is involved in melanosome maturation, including melanogenesis, melanosome biogenesis, and melanin polymerization.
The expression of the PMEL gene is regulated by the microphthalmia-associated transcription factor (MITF).
Clinical significance
The gp100 protein is a melanoma antigen, i.e. a tumor-associated antigen.
The gp100 protein contains differentiation antigens and has been widely studied as a target for melanoma immunotherapy. Different sequences of the GP100 peptide could be used for immunization against tumors. According to a case study, modifications of GP100, such as GP100-209 and GP100-208, have shown a greater number of antigen-specific CTL's (cytotoxic T lymphocytes), which can target and kill cancer cells.
Short fragments of PMEL have been used to develop the gp100 cancer vaccine which is or contains gp100:209-217(210M).
Hydrophilic recombinant gp100 protein (HR-gp100) has been topically applied on human intact skin in vitro, and used as a vaccine in a mouse model. It was demonstrated that HR-gp100 permeates into human skin, and is processed and presented by human dendritic cells. In the mouse model, an HR-gp100-based vaccine triggered antigen-specific T cell responses, as shown by proliferation assays, ELISA and intracellular staining for IFN-γ.
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000185664 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025359 – 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.
- ↑ Kim KK, Youn BS, Heng HH, Shi XM, Tsui LC, Lee ZH, et al. (October 1996). "Genomic organization and FISH mapping of human Pmel 17, the putative silver locus". Pigment Cell Research. 9 (1): 42–48. doi:10.1111/j.1600-0749.1996.tb00085.x. PMID 8739560.
- ↑ "Entrez Gene: SILV silver homolog (mouse)".
- 1 2 3 4 5 Watt B, van Niel G, Raposo G, Marks MS (May 2013). "PMEL: a pigment cell-specific model for functional amyloid formation". Pigment Cell & Melanoma Research. 26 (3): 300–315. doi:10.1111/pcmr.12067. PMC 3633693. PMID 23350640.
- 1 2 Theos AC, Watt B, Harper DC, Janczura KJ, Theos SC, Herman KE, et al. (July 2013). "The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB". Pigment Cell & Melanoma Research. 26 (4): 470–486. doi:10.1111/pcmr.12084. PMC 3695043. PMID 23452376.
- ↑ Hee JS, Mitchell SM, Liu X, Leonhardt RM (March 2017). "Melanosomal formation of PMEL core amyloid is driven by aromatic residues". Scientific Reports. 7 44064. doi:10.1038/srep44064. PMC 5341037. PMID 28272432.
- ↑ Rochin L, Hurbain I, Serneels L, Fort C, Watt B, Leblanc P, et al. (June 2013). "BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells". Proceedings of the National Academy of Sciences of the United States of America. 110 (26): 10658–10663. doi:10.1073/pnas.1220748110. PMC 3696817. PMID 23754390.
- 1 2 Kummer MP, Maruyama H, Huelsmann C, Baches S, Weggen S, Koo EH (January 2009). "Formation of Pmel17 amyloid is regulated by juxtamembrane metalloproteinase cleavage, and the resulting C-terminal fragment is a substrate for gamma-secretase". The Journal of Biological Chemistry. 284 (4): 2296–2306. doi:10.1074/jbc.M808904200. PMC 2629115. PMID 19047044.
- ↑ Wolfe MS (April 2009). "Intramembrane proteolysis". Chemical Reviews. 109 (4): 1599–1612. doi:10.1021/cr8004197. PMC 2667872. PMID 19226105.
- 1 2 3 Eisenberg G, Machlenkin A, Frankenburg S, Mansura A, Pitcovski J, Yefenof E, et al. (2010). "Transcutaneous immunization with hydrophilic recombinant gp100 protein induces antigen-specific cellular immune response". Cellular Immunology. 266 (1): 98–103. doi:10.1016/j.cellimm.2010.09.003. PMC 2976976. PMID 20947070.
- 1 2 3 Bianchi V, Bulek A, Fuller A, Lloyd A, Attaf M, Rizkallah PJ, et al. (April 2016). "A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen". The Journal of Biological Chemistry. 291 (17): 8951–8959. doi:10.1074/jbc.M115.707414. PMC 4861463. PMID 26917722.
- ↑ Du J, Miller AJ, Widlund HR, Horstmann MA, Ramaswamy S, Fisher DE (2003). "MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma". The American Journal of Pathology. 163 (1): 333–343. doi:10.1016/S0002-9440(10)63657-7. PMC 1868174. PMID 12819038.
- ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
- ↑ "NCI Drug Dictionary". National Cancer Institute.
Further reading
- Aplan PD, Lombardi DP, Kirsch IR (1991). "Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia". Molecular and Cellular Biology. 11 (11): 5462–5469. doi:10.1128/mcb.11.11.5462. PMC 361915. PMID 1922059.
- Kwon BS, Chintamaneni C, Kozak CA, Copeland NG, Gilbert DJ, Jenkins N, et al. (October 1991). "A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12". Proceedings of the National Academy of Sciences of the United States of America. 88 (20): 9228–9232. Bibcode:1991PNAS...88.9228K. doi:10.1073/pnas.88.20.9228. PMC 52687. PMID 1924386.
- Brown L, Cheng JT, Chen Q, Siciliano MJ, Crist W, Buchanan G, et al. (October 1990). "Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia". The EMBO Journal. 9 (10): 3343–3351. doi:10.1002/j.1460-2075.1990.tb07535.x. PMC 552072. PMID 2209547.
- van Niel G, Bergam P, Di Cicco A, Hurbain I, Lo Cicero A, Dingli F, et al. (October 2015). "Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells". Cell Reports. 13 (1): 43–51. doi:10.1016/j.celrep.2015.08.057. PMID 26387950.
- Adema GJ, de Boer AJ, Vogel AM, Loenen WA, Figdor CG (August 1994). "Molecular characterization of the melanocyte lineage-specific antigen gp100". The Journal of Biological Chemistry. 269 (31): 20126–20133. doi:10.1016/S0021-9258(17)32136-1. hdl:2066/27146. PMID 7519602.
- Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, et al. (July 1994). "Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection". Proceedings of the National Academy of Sciences of the United States of America. 91 (14): 6458–6462. Bibcode:1994PNAS...91.6458K. doi:10.1073/pnas.91.14.6458. PMC 44221. PMID 8022805.
- Maresh GA, Marken JS, Neubauer M, Aruffo A, Hellström I, Hellström KE, et al. (February 1994). "Cloning and expression of the gene for the melanoma-associated ME20 antigen". DNA and Cell Biology. 13 (2): 87–95. doi:10.1089/dna.1994.13.87. PMID 8179825.
- Bailin T, Lee ST, Spritz RA (1996). "Genomic organization and sequence of D12S53E (Pmel 17), the human homologue of the mouse silver (si) locus". The Journal of Investigative Dermatology. 106 (1): 24–27. doi:10.1111/1523-1747.ep12326976. PMID 8592076.
- Chakraborty AK, Platt JT, Kim KK, Kwon BS, Bennett DC, Pawelek JM (February 1996). "Polymerization of 5,6-dihydroxyindole-2-carboxylic acid to melanin by the pmel 17/silver locus protein". European Journal of Biochemistry. 236 (1): 180–188. doi:10.1111/j.1432-1033.1996.t01-1-00180.x. PMID 8617263.
- Chi DD, Merchant RE, Rand R, Conrad AJ, Garrison D, Turner R, et al. (June 1997). "Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas". The American Journal of Pathology. 150 (6): 2143–2152. PMC 1858329. PMID 9176405.
- Wagner SN, Wagner C, Schultewolter T, Goos M (1997). "Analysis of Pmel17/gp100 expression in primary human tissue specimens: implications for melanoma immuno- and gene-therapy". Cancer Immunology, Immunotherapy. 44 (4): 239–247. doi:10.1007/s002620050379. PMC 11037831. PMID 9222283. S2CID 24294029.
- Curry BJ, Myers K, Hersey P (1998). "Polymerase chain reaction detection of melanoma cells in the circulation: relation to clinical stage, surgical treatment, and recurrence from melanoma". Journal of Clinical Oncology. 16 (5): 1760–1769. doi:10.1200/JCO.1998.16.5.1760. PMID 9586889.
- Lupetti R, Pisarra P, Verrecchia A, Farina C, Nicolini G, Anichini A, et al. (September 1998). "Translation of a retained intron in tyrosinase-related protein (TRP) 2 mRNA generates a new cytotoxic T lymphocyte (CTL)-defined and shared human melanoma antigen not expressed in normal cells of the melanocytic lineage". The Journal of Experimental Medicine. 188 (6): 1005–1016. doi:10.1084/jem.188.6.1005. PMC 2212536. PMID 9743519.
- Lukowsky A, Bellmann B, Ringk A, Winter H, Audring H, Fenske S, et al. (October 1999). "Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction". The Journal of Investigative Dermatology. 113 (4): 554–559. doi:10.1046/j.1523-1747.1999.00719.x. PMID 10504440.
- Raposo G, Tenza D, Murphy DM, Berson JF, Marks MS (February 2001). "Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells". The Journal of Cell Biology. 152 (4): 809–824. doi:10.1083/jcb.152.4.809. PMC 2195785. PMID 11266471.
- Virador V, Matsunaga N, Matsunaga J, Valencia J, Oldham RJ, Kameyama K, et al. (August 2001). "Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions". Pigment Cell Research. 14 (4): 289–297. doi:10.1034/j.1600-0749.2001.140410.x. PMID 11549113.
- Berson JF, Harper DC, Tenza D, Raposo G, Marks MS (November 2001). "Pmel17 initiates premelanosome morphogenesis within multivesicular bodies". Molecular Biology of the Cell. 12 (11): 3451–3464. doi:10.1091/mbc.12.11.3451. PMC 60267. PMID 11694580.
- Sensi M, Pellegatta S, Vegetti C, Nicolini G, Parmiani G, Anichini A (April 2002). "Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones". Tissue Antigens. 59 (4): 273–279. doi:10.1034/j.1399-0039.2002.590404.x. PMID 12135425.