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 PMELgene.[5][6] Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
Structure and function
PMEL is a 100 kDa, 661 amino acids long 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.
This protein is involved in melanosome maturation, including melanogenesis, melanosome biogenesis, and melanin polymerization (Eisenberg) [1]. 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.
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.
The gp100 protein contains differentiation antigens.[2], and has been widely studied to be used 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 (Eisenberg).[3]
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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". J. Clin. Oncol. 16 (5): 1760–9. doi:10.1200/JCO.1998.16.5.1760. PMID9586889.
Virador V, Matsunaga N, Matsunaga J, et al. (2002). "Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions". Pigment Cell Res. 14 (4): 289–97. doi:10.1034/j.1600-0749.2001.140410.x. PMID11549113.
