TYROSINASE-RELATED PROTEIN-1 (TRP1) FUNCTIONS AS A DHICA OXIDASE IN MELANIN BIOSYNTHESIS

Several genes critical to the enzymatic regulation of melanin producti on in mammals have recently been cloned and mapped to the albino, brow n and slaty loci in mice. All three genes encode proteins with similar structures and features, but with distinct catalytic capacities; the functions of two of those gene products have previously been identifie d. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, while the slaty locus encodes tyrosinase-relate d protein 2 (TRP2), an enzyme with a single specific, but distinct, fu nction as DOPAchrome tautomerase. Although the brown locus, encoding T RP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of bl ack rather than brown melanin) has been in general dispute. In this st udy we have used two different techniques (expression of TRP1 in trans fected fibroblasts and immunoaffinity purification of TRP1 from melano cytes) to examine the enzymatic function(s) of TRP1. The data demonstr ate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indol e-quinone at a downstream point in the melanin biosynthetic pathway. T his enzyme activity appears to be essential to the further metabolism of DHICA to a high molecular weight pigmented biopolymer.