A Novel Splice Variant of Pmel17 Expressed by Human Melanocytes and Melanoma Cells Lacking Some of the Internal Repeats
| Autor: | Sarah E. Nichols, Dawn C. Harper, Michael S. Marks, Joanne F. Berson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Skin Neoplasms
Immunoprecipitation RNA Splicing T-Lymphocytes Molecular Sequence Data melanosome Dermatology Melanocyte Biology Biochemistry Article Epitopes 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Complementary DNA medicine Humans Direct repeat silver Amino Acid Sequence RNA Messenger Melanoma Molecular Biology 030304 developmental biology Melanins chemistry.chemical_classification 0303 health sciences Melanosomes Membrane Glycoproteins Base Sequence fibril formation Alternative splicing Intron Proteins Cell Biology Molecular biology Protein Structure Tertiary 3. Good health gp100 medicine.anatomical_structure chemistry Tandem Repeat Sequences 030220 oncology & carcinogenesis RNA splicing Melanocytes Glycoprotein gp100 Melanoma Antigen |
| Zdroj: | Journal of Investigative Dermatology. 121:821-830 |
| ISSN: | 0022-202X |
| Popis: | Pmel17 is a approximately 100 kDa pigment cell specific glycoprotein that plays a crucial part in the morphogenesis of melanosome precursors. Anti-Pmel17 immunoprecipitates from metabolically pulse labeled melanoma cells and melanocytes contain, in addition to full-length Pmel17, a glycoprotein that migrates with a lower relative molecular weight. Here we show that this glycoprotein is encoded by an mRNA that results from alternative splicing of the human Pmel17 gene from which a cryptic intron is excised. Immunoprecipitation recapture experiments showed that this glycoprotein contained both the N- and C-termini of full-length Pmel17. Sequence analysis of cDNA corresponding to the alternatively spliced form reveals the loss of three of 10 imperfect direct repeats from the central region of the lumenal domain. The product of the splice variant is processed with similar kinetics to full-length Pmel17, and localizes similarly to late endosomes when expressed ectopically in nonpigment cells. We speculate that truncation of the repeat region within Pmel17 alters either fibrillogenic activity or the interaction of Pmel17 with melanin intermediates. The expression of an alternatively spliced product may furthermore affect the cohort of peptides generated for recognition of melanoma cells by tumor-directed T lymphocytes. |
| Databáze: | OpenAIRE |
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