Abstract
The hues of mammalian skin and hair vary from white to jet black. Silvers has recently catalogued over 130 different coat colour mutations at more than 50 genetic loci in the house mouse (Mus musculus), a useful model for study1. Some of these loci govern differentiation of melanocytes and their migration from the neural crest region during embryogenesis2. Others, however, involve expression of genes for melanin synthesis within the pigment cell, such as c-locus mutations, where animals are phenotypically albino, c-locus albinism is presumably due to a deficiency of active tyrosinase, the enzyme catalysing the initial steps in the melanin synthetic pathway. It has generally been assumed that the only regulated steps in this pathway are those governed by tyrosinase, since in vitro, melanin is spontaneously formed from dopa quinone (Fig. 1). However, Logan and Weatherhead have provided evidence for post-tyrosinase inhibition of melanogenesis by melatonin in hair follicles of Siberian hamsters5, as do our studies with various mutants of Cloudman mouse melanoma cells, suggesting the involvement of a second regulatory site. We describe here three new factors which control melanin synthesis that we have partially purified from Cloudman cells: (1) dopachrome conversion factor (DCF), which accelerates the conversion of dopachrome to 5,6-dihydroxyindole (see ref. 6 for detailed description); (2) 5,6-dihydroxindole conversion factor, which catalyses the conversion of 5,6-dihydroxyindole to melanin and is active only when cells are exposed to melanotropin (MSH), and (3) 5,6-dihydroxyindole blocking factor, which restricts melanogenesis at 5,6-dihydroxyindole. This third factor appears to protect cells from the cytotoxic effects of melanin precursors, and it is removed when the cells are exposed to MSH. Discovery of the factors indicates that regulation of the melanin biosynthetic pathway is more complex than previously supposed.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Silvers, W. K. The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction (Springer, Berlin, 1979).
Rawles, M. E. Physiol. Rev. 28, 383–408 (1948).
Mason, H. S. Adv. Enzym. 16, 105–184 (1955).
Hempel, K. in Structure and Control of the Melanocyte (eds Della Porta, G. & Muhlbock, O.) 162–175 (Springer, Berlin, 1966).
Logan, A. & Weatherhead, B. J. invest. Derm. 71, 295–298 (1978).
Körner, A. & Pawelek, J. J. invest. Derm, (in the press).
Greene, H. S. N. Cancer Res. 18, 122–125 (1958).
Pawelek, J. et al. Proc. natn. Acad. Sci. U.S.A. 72, 951–955 (1975).
Bradford, M. Analyt. Biochem. 72, 248–254 (1976).
Mason, H. S. J. biol Chem. 172, 83–99 (1948).
Axelrod, J. & Lerner, A. B. Biochim. biophys. Acta 71, 650–655 (1963).
Lerner, A. B. Am. J. Med. 52, 141–148 (1971).
Pawelek, J. J. invest. Derm. 66, 201–209 (1976).
Pawelek, J. & Lerner, A. B. Nature 276, 627–628 (1978).
Wick, M. M. J. invest. Derm. 74, 63–65 (1980).
King, R. A., Olds, D. P. & Witcop, C. J. Pigment Cell 5, 16–20 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pawelek, J., Körner, A., Bergstrom, A. et al. New regulators of melanin biosynthesis and the autodestruction of melanoma cells. Nature 286, 617–619 (1980). https://doi.org/10.1038/286617a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/286617a0
This article is cited by
-
Function-blocking autoantibodies to the melanin-concentrating hormone receptor in vitiligo patients
Laboratory Investigation (2006)
-
Enhancement of pulmonary metastasis formation and ?-glutamyltranspeptidase activity in B16 melanoma induced by differentiation in vitro
Clinical & Experimental Metastasis (1993)
-
Light is a dominant mouse mutation resulting in premature cell death
Nature Genetics (1992)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.