The function of MITF and associated proteins in mast cells

Mutation of microphthalmia transcription factor (MITF) results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. The primary cell types affected in MITF-deficient mice are melanocytes, osteoclasts and mast cells. A search for MITF-associated proteins, using a mast cell library that was screened with a construct that encodes the basic helix-loop-helix leucine zipper (bHLH-Zip) domain of MITF, resulted in the isolation of the protein kinase C interacting (PKCI) protein 1 and protein inhibitor of activated STAT3 (PIAS3). We have accumulated clear evidence of a function for these two proteins as repressors of MITF-induced transcriptional activity. Here, we describe this evidence and ideas that give some insight into the cellular network of interactions between various transcription factors and MITF.