Tamas, Macrophage MigrationInhibitory Factor (MIF) tautomerase
inhibitors aspotential novel anti-inflammatory agents:Current Developments, Curr.
Among the genes of the tyrosinase-related protein (TYRP) family, dopachrome tautomerase
(DCT) plays important roles in the melanin pigmentation of vertebrates .
A spontaneous coat colour variant nm2798 is caused by the dopachrome tautomerase
(Dct) allele Dctslt4t3J and is associated with iris pigment dispersion .
Melanocytes with a positive expression of TRP-2 (tautomerase
dopachrome) are considered to be melanocyte precursors, but TRP-1 positive is considered to be diverse and mature [37, 38].
Other reactions are mediated by tyrosinase-related protein (TRP1) and dopachrome tautomerase
(DCT) that catalyze the tautomerization of indolene-2-carboxylic acid-5, 6-quinone or dopachrome and oxidation of 5,6-dihydroxylindole-2-carboxylic acid, respectively .
Mechanisms involved in CEACAM1 and MITF correlation in melanoma may involve sex determining region Y [SRY] related HMG-box 9 (SOX9); SOX9 is a transcription factor involved in chondrogenesis and sex determination in embryo ; its function in normal melanocytes is upregulation of melanin synthesis in melanocytic cells after ultraviolet B (shortwave) rays (UVB) exposure by increasing MITF, dopachrome tautomerase
(tyrosine-related protein 2), and tyrosinase expression , while increased expression of SOX9 in melanoma inhibits tumor cell proliferation by binding p21 directly or via MITF [48, 49].
Both TYRP-1 and TYRP-2 (also called DOPAchrome tautomerase
, DCT) are involved in the downstream reactions of the melanogenic pathway, aMelanocyte stimulating hormone ([alpha]-MSH), a physiological ligand that binds and acts on the G protein-coupled melanocortin 1 receptor (MC1R), potently activates the microphthalmia-associated transcription factor (MITF) to increase the expression of tyrosinase and the melanogenic enzymes TYRP-1 and TYRP-2, which ultimately induce melanin synthesis (Costin and Hearing, 2007; Park et al., 2009).
The ink gland has been also shown to contain a variety of melanogenic enzymes as tyrosinase, dopachrome tautomerase
, and peroxidase .
Different experimental strategies, including anti-MIF antibodies and knockout (KO) and transgenic MIF mice (MIF-Tg), have been used to establish that MIF counterregulates the immunosuppressive effects of steroids and to implicate MIF in tumor necrosis factor (TNF[alpha]) and nitric oxide (NO) production ; additionally, MIF was found to possess growth factor activity , overregulate the expression of Toll-like receptor (TLR)-4 on antigen-presenting cells , sustain macrophage proinflammatory abilities by inhibiting p53, and also possess tautomerase
and oxidoreductase activities .
 cloned and expressed seven genes, cnbA, cnbB, cnbCa, cnbCb, cnbD, cnbG, and cnbH, in recombinant Escherichia coli, which were identified as encoding 4CNB-nitroreductase (CnbA), 1-hydroxylaminobenzene mutase (CnbB), 2-aminophenol 1,6-dioxygenase (CnbCab), 2-amino-5-chloromuconic semialdehyde dehydrogenase (CnbD), 2-hydroxy-5-chloromuconic acid tautomerase
, and 2-amino-5-chloromuconic acid deaminase (CnbH).
Very recently, the protein D-dopachrome tautomerase
(D-DT), which is the only known MIF homolog in the human genome, was identified as a cytokine [82, 175].
Plant-derived anti-inflammatory compounds affect MIF tautomerase