Mast Cells Provide a “HINT” to the Function of an Exotic Nucleotide

One or more members of the HIT (histidine triad) family of proteins is encoded in the genomes of diverse species, ranging from prokaryotes to humans. However, the precise cellular and biochemical functions of many of these proteins are largely enigmatic . Therefore, the paper by Lee et al. in this issue of Immunity that ascribes a role for the histidine triad protein HINT (also designated HINT1) in regulating the activity of the microphthalmia transcription factor (MITF) is of great interest. Furthermore, this study implicates a role for an exotic endogenous nucleotide Ap4A in this process. This naturally occurring compound consists of two adenosines linked by four phosphate residues, and has been proposed as an intracellular and extracellular signaling molecule . [Copyright &y& Elsevier]