Qualitative and Quantitative Catalog of Tyrosinase Alternative Transcripts in Normal Murine Skin Melanocytes as a Basis for Detecting Melanoma-Specific Changes

Kelsall, Stephen R.; Fur, Nathalie Le; Mintz, Beatrice

doi:10.1006/bbrc.1997.6925

Cited by 13 publications

(6 citation statements)

References 16 publications

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“…The major band, of higher molecular size, was identical with the published wild-type sequence of the mouse enzyme ( [31], GenBank accession number D00440). The minor band, of smaller size, corresponded to an alternative splicing variant whose occurrence has been reported by others [32]. This form, called ∆3tyr, lacks exon 3, between positions 1037 and 1184 of the coding sequence, thus generating a frameshift and a premature stop codon.…”

Section: Transient Expression Of Human and Mouse Tyrosinase In Cos7 Csupporting

confidence: 54%

The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

Olivares

Jiménez‐Cervantes

Lozano

et al. 2001

Biochemical Journal

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Melanin synthesis in mammals is catalysed by at least three enzymic proteins, tyrosinase (monophenol dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and tyrosinase-related proteins (tyrps) 1 and 2, whose genes map to the albino, brown and slaty loci in mice, respectively. Tyrosinase catalyses the rate-limiting generation of l-dopaquinone from l-tyrosine and is also able to oxidize l-dopa to l-dopaquinone. Conversely, mouse tyrp1, but not tyrosinase, catalyses the oxidation of the indolic intermediate 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into the corresponding 5,6-indolequinone-2-carboxylic acid, thus promoting the incorporation of DHICA units into eumelanin. The catalytic activities of the human melanogenic enzymes are still debated. TYRP1has been reported to lack DHICA oxidase activity, whereas tyrosinase appears to accelerate DHICA consumption, thus raising the question of DHICA metabolism in human melanocytes. Here we have used two different approaches, comparison of the catalytic activities of human melanocytic cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, and transient expression of TYR and tyr genes in COS7 cells, to demonstrate that human tyrosinase actually functions as a DHICA oxidase, as opposed to the mouse enzyme. Therefore, human tyrosinase displays a broader substrate specificity than its mouse counterpart, and might be at least partially responsible for the incorporation of DHICA units into human eumelanins.

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Section: Transient Expression Of Human and Mouse Tyrosinase In Cos7 Csupporting

confidence: 54%

The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

Olivares

Jiménez‐Cervantes

Lozano

et al. 2001

Biochemical Journal

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“…Similar transcript variants of the tyrosinase gene have been identi®ed in mouse skin melanocytes and melanoma, and these transcripts do not result in active tyrosinase protein (Porter et al, 1991;Mu Èller et al, 1988;Ruppert et al, 1988;Le Fur et al, 1996;Kelsall et al, 1997). In the mouse, exon 1 contains two alternative donor splice sites (at bp 291 and 369) and two alternative receptor splice sites (at bp 522 and 858); the normal splice site at the 3¢ end of exon 1 is at bp 881 (Kelsall et al, 1997). The locations of the alternative splice sites in the mouse are similar to but not identical to those that produce alternative transcripts in human lymphoblastoid cell line mRNA.…”

Section: Discussionmentioning

confidence: 67%

“…These transcripts are presumably degraded rather than processed in these cells as there is no evidence that they are involved in melanin synthesis. Similar transcript variants of the tyrosinase gene have been identi®ed in mouse skin melanocytes and melanoma, and these transcripts do not result in active tyrosinase protein (Porter et al, 1991;Mu Èller et al, 1988;Ruppert et al, 1988;Le Fur et al, 1996;Kelsall et al, 1997). In the mouse, exon 1 contains two alternative donor splice sites (at bp 291 and 369) and two alternative receptor splice sites (at bp 522 and 858); the normal splice site at the 3¢ end of exon 1 is at bp 881 (Kelsall et al, 1997).…”

Section: Discussionmentioning

confidence: 73%

Alternative Splicing of the Tyrosinase Gene Transcript in Normal Human Melanocytes and Lymphocytes

Fryer

Oetting

Brott

et al. 2001

Journal of Investigative Dermatology

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We have identified and isolated ectopically expressed tyrosinase transcripts in normal human melanocytes and lymphocytes and in a human melanoma (MNT-1) cell line to establish a baseline for the expression pattern of this gene in normal tissue. Tyrosinase mRNA from human lymphoblastoid cell lines was reverse transcribed and amplified using specific "nested" primers. This amplification yielded eight identifiable transcripts; five that resulted from alternative splicing patterns arising from the utilization of normal and alternative splice sequences. Identical splicing patterns were found in transcripts from human primary melanocytes in culture and a melanoma cell line, indicating that lymphoblastoid cell lines provide an accurate reflection of transcript processing in melanocytes. Similar splicing patterns have also been found with murine melanocyte tyrosinase transcripts. Our results demonstrate that alternative splicing of human tyrosinase gene transcript produces a number of predictable and identifiable transcripts, and that human lymphoblastoid cell lines provide a source of ectopically expressed transcripts that can be used to study the biology of tyrosinase gene expression in humans.

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“…The study of mRNA biogenesis in the last few years has revealed an elaborate surveillance mechanism involving factors such as the UPF proteins that culls aberrantly spliced mRNAs and mRNAs with premature termination codons. There might be a hint that such RNA quality control mechanisms go awry in cancers, just as DNA quality control mechanisms do, where aberrantly spliced transcripts accumulate in a tumor [20]. Now that the gates are open, we may have a flood of studies on RNome stability and cancer.…”

Section: Rnome Stability: a Link To Cancer?mentioning

confidence: 99%

RNA Repair: Damage Control

Bellacosa

Moss

2003

Current Biology

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Qualitative and Quantitative Catalog of Tyrosinase Alternative Transcripts in Normal Murine Skin Melanocytes as a Basis for Detecting Melanoma-Specific Changes

Cited by 13 publications

References 16 publications

The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

Alternative Splicing of the Tyrosinase Gene Transcript in Normal Human Melanocytes and Lymphocytes

RNA Repair: Damage Control

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