A murine monoclonal antibody, MoAb HMSA-5, against a melanosomal component highly expressed in early stages, and common to normal and neoplastic melanocytes

Der, J. E.; Dixon, Walter T.; Jimbow, Kowichi; Horikoshi, Tsutomu

doi:10.1038/bjc.1993.8

Cited by 19 publications

(20 citation statements)

References 41 publications

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“…To determine the melanogenesis-protein synthesis of transfected cells, proteins isolated from the transfectants were resolved by SDS-PAGE and identified by immunoprecipitation with monoclonal antibodies against tyrosinase (aPEP7) (23) and TRP-I (HMSA-5) (24). In contrast to the results from a negative control ofvector-transfectants, COS-7 cells and amelanotic cells transfected with human tyrosinase cDNA or co-transfected with both human tyrosinase and TRP-l cDNAs produced tyrosinase protein with an approximate molecular mass of 68 kDa, identical in size to human tyrosinase.…”

Section: Gene and Protein Expressions Of Human Tyrosinase And Lamp Famentioning

confidence: 99%

Molecular Control of Melanogenesis in Malignant Melanoma: Functional Assessment of Tyrosinase and Lamp Gene Families by UV Exposure and Gene Co‐Transfection, and Cloning of a cDNA Encoding Calnexin, A Possible Melanogenesis “Chaperone”

Jimbow

Hara

Vinayagamoorthy

et al. 1994

The Journal of Dermatology

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Melanogenesis is a cascade of events significantly controlled by regulatory genes which are associated with the melanosomal membrane. This report introduces our current research efforts dealing with (a) the gene and protein expressions of tyrosinase and Lamp (lysosome-associated membrane protein) families by human melanoma cells after repeated exposures to UV light, (b) the coordinated alterations in the expression of the Lamp family gene and its encoding product after transfection of two genes of the tyrosinase family in human melanoma cells and (c) cloning and sequencing of a Ca(2+)-binding phosphoprotein, calnexin, which could be a candidate as a chaperone for sorting and maturation of tyrosinase and Lamp family glycoproteins in melanogenesis cascade. Our UV exposure study, as well as gene transfection and antisense hybridization experiments, has clearly indicated a marked and coordinated interaction of the Lamp-1 gene with the tyrosinase and TRP-1 genes in this process. We propose that melanogenesis is controlled at least by two major gene family products, i.e., (a) the tyrosinase family of tyrosinase, TRP-1 and TRP-2, and the Lamp family of Lamp-1, Lamp-2 and Lamp-3. These two gene families probably derived from primordial melanogenesis-associated genes which are common or closely related to each other.

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Section: Gene and Protein Expressions Of Human Tyrosinase And Lamp Famentioning

confidence: 99%

Molecular Control of Melanogenesis in Malignant Melanoma: Functional Assessment of Tyrosinase and Lamp Gene Families by UV Exposure and Gene Co‐Transfection, and Cloning of a cDNA Encoding Calnexin, A Possible Melanogenesis “Chaperone”

Jimbow

Hara

Vinayagamoorthy

et al. 1994

The Journal of Dermatology

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“…38 of TRP-1 expression was seen after treatment of tunica mycin (Fig 6). 41 The findings clearly indicated that TRP -1 is transferred from ER to the medial portion of the Golgi complex where full glycosylation may be completed . On the other hand, tyrosinase will be processed during glycosylation to the periphery of the Golgi network, trans-Golgi network, and then subsequently transferred In contrast, tyrosinase is present in the trans-Golgi network and the coated vesicles and melanosomes in late stages of 2, 3, and 4.…”

Section: Photoprotective Vs Phototoxic Actions Of Melanin Pigmentsmentioning

confidence: 86%

Current Update and Trends in Melanin Pigmentation and Melanin Biology.

Jimbow

1995

Keio j. med

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Abstract. Certain aspects of current progress in melanin biology and its possible clinical relevances are reviewed with emphasis on some of our recent research activities. The important aspects discussed are (a) the biological properties of melanin pigments and their relevance to biological functions, (b) functional interaction of melanogenic/melanogenesis-associated genes in melanin biosynthesis process (melanogenesis, and (c) the targeting of proteins involved in melanogenesis and assembly by melanosomal proteins. Upon exposure to UV light radiation (UVR), melanin pigments revealed two distinct photobiological reactions, i.e. photoprotective and phototoxic reactions. The precursor intermediate of brown-black eumelanin, 5-6-dihydroxyindole, appears to possess the most potent photoprotective (antioxidant) property. Eumelanin pigment also had some antioxidant property. Similarly, yellow-red pheomelanin and its precursor intermediate, 5-S-cysteinyldopa also revealed some antioxidant property, but they became prooxidant in the presence of the ferric iron upon exposure to UVR. Melanosomes are known to possess several metal ions including Fe2+, Fe3+, Cu2+ and Zn2+. In addition, upon exposure to UV-light, there is an increase in ferric/ferrous iron in the skin. Therefore, in the in vivo system, pheomelanin intermediate, 5-S cysteinyldopa, may show significant prooxidant property in conjunction with metal ions (e.g. Fe2+, Fe3+). When atypical moles (previously called dysplastic nevi) were analysed chemically for quantitative and qualitative properties of melanin pigment, they revealed a high ratio of pheomelanin/eumelanin content. This finding may partly explain our clinical observation that these moles are frequently the precursors of malignant melanoma and that the intermittent heavy exposure of UVR can be the major direct cause of their transformation. How, then, the melanosomal compartment, where active new melanin synthesis occurs after exposure to UVR, is protected from the cytotoxicity of melanin precursor intermediates. To study this question, two major experiments were conducted; (a) expression of melanogenesis-associated genes upon exposure of melanocytes to UVR and (b) transfection of cDNAs from the melanogenesis associated genes. There was coordinated gene expression (mRNA) of tyrosinase and tyrosinase-related protein, TRP-1 and this coordinated gene expression was also accompanied by the upregulation of LAMP-1 (lysosome-associated membrane protein-1). Furthermore, human tyrosinase and TRP-1 mRNAs were expressed successfully in individual transfectants or co-transfectants of cDNAs from the two genes. Co-transfectants of human tyrosinase and TRP-1 cDNAs produced many lysosomal granules and melanin-containing granules, melanosomes. LAMP-1 gene was upregulated simultaneously in co-transfectants of tyrosinase and TRP-1, but not in individual transfectants of the two genes. TRP-1 and LAMP-1 gene products were transferred from Golgi complexes to melanosomes. LAMP-1 gene products stimulated by TRP-1 and tyrosinase...

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“…At the end of the chase time cell lysates were immunoprecipitated with ␣PEP1 antiserum and analyzed in reducing SDS-PAGE to monitor the maturation of the folding intermediates (lanes 1-4). In a control experiment TRP-1 maturation in untreated cells, at 0, 15, 45, and 60 min of chase, was analyzed (lanes [5][6][7][8]. TRP-1 immunoprecipitated from cells where DTT was added immediately after pulse or after 15 min and chased for 45 min migrates as a partially glycosylated precursor of approximately 69 kDa (lanes 1 and 2).…”

Section: Trp-1 Folding In B16 Mousementioning

confidence: 99%

“…TRP-1 or glycoprotein 75 is the most abundant glycoprotein in melanocytes (2,3) and one of the best characterized melanoma antigens (4,5). It is well known that TRP-1 has an important role in the maturation and stability of melanosomes, site organelles of the melanin synthesis and deposition (5,6). TRP-1 maps to the brown locus on chromosome 4 (7,8).…”

mentioning

confidence: 99%

Folding and Maturation of Tyrosinase-related Protein-1 Are Regulated by the Post-translational Formation of Disulfide Bonds and by N-Glycan Processing

Negroiu¹,

Dwek²,

Petrescu³

2000

Journal of Biological Chemistry

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In this study we have explored the endoplasmic reticulum associated events accompanying the maturation of the tyrosinase-related protein-1 (TRP-1) nascent chain synthesized in mouse melanoma cells. We show that TRP-1 folding process occurs much more rapidly than for tyrosinase, a highly homologous protein, being completed post-translationally by the formation of critical disulfide bonds. In cells pretreated with dithiothreitol (DTT), unfolded TRP-1 is retained in the endoplasmic reticulum by a prolonged interaction with calnexin and BiP before being targeted for degradation. The TRP-1 chain was able to fold into DTT-resistant conformations both in the presence or absence of ␣-glucosidase inhibitors, but folding occurred through different pathways. During the normal folding pathway, TRP-1 interacts with calnexin. In the presence of ␣-glucosidase inhibitors, the interaction with calnexin is prevented, with TRP-1 folding being assisted by BiP. In this case, the process has similar kinetics to that of untreated TRP-1 and yields a compact form insensitive to DTT as well. However, this form has different thermal denaturation properties than the native conformation. We conclude that disulfide bridge burring is crucial for the TRP-1 export. This suggests that although various folding pathways may complete this process, the native form may be acquired only through the normal unperturbed pathway.

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A murine monoclonal antibody, MoAb HMSA-5, against a melanosomal component highly expressed in early stages, and common to normal and neoplastic melanocytes

Cited by 19 publications

References 41 publications

Molecular Control of Melanogenesis in Malignant Melanoma: Functional Assessment of Tyrosinase and Lamp Gene Families by UV Exposure and Gene Co‐Transfection, and Cloning of a cDNA Encoding Calnexin, A Possible Melanogenesis “Chaperone”

Molecular Control of Melanogenesis in Malignant Melanoma: Functional Assessment of Tyrosinase and Lamp Gene Families by UV Exposure and Gene Co‐Transfection, and Cloning of a cDNA Encoding Calnexin, A Possible Melanogenesis “Chaperone”

Current Update and Trends in Melanin Pigmentation and Melanin Biology.

Folding and Maturation of Tyrosinase-related Protein-1 Are Regulated by the Post-translational Formation of Disulfide Bonds and by N-Glycan Processing

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