Activating mutations in codon D816 of the tyrosine kinase receptor, KIT, are found in the majority of patients with systemic mastocytosis. We found that the transcription factor, microphthalmia-associated transcription factor (MITF), is highly expressed in bone marrow biopsies from 9 of 10 patients with systemic mastocytosis and activating c-KIT mutations. In primary and transformed mast cells,...

The mi transcription factor (MITF) is a basic-helix-loop-helix-leucine zipper transcription factor that is important for the development of mast cells. Cultured mast cells (CMCs) of mi/mi genotype express abnormal MITF (mi-MITF), but CMCs of tg/tg genotype do not express any MITFs. It was previously reported that mi/mi CMCs showed more severe abnormalities than tg/tg CMCs, indicating that mi-MI...

Microphthalmia-associated transcription factor (MITF), a key regulator of melanocyte development, belongs to the class of basic-helix ⁄ loop ⁄ helixleucine-zipper transcription factors. Microphthalmia-associated transcription factor regulates multiple genes related to melanin synthesis (e.g. TYR, DCT), control of apoptosis (e.g. BCL2) and cell cycle progression (e.g. p21, p16, CDK2, TBX2) as we...

Waardenburg syndrome (WS) is an inherited sensorineural deafness condition in humans caused by melanocyte deficiencies in the inner ear and forelock. Mutation of microphthalmia-associated transcription factor (MITF) is known to produce WS type IIA whereas mutations of either endothelin (EDN) or its receptor endothelin receptor B (EDNRB) produce WS type IV. However, a link between MITF haploinsu...

The more than 20 different Mitf mutations in the mouse are all associated with deficiencies in neural crest-derived melanocytes that range from minor functional disturbances with some alleles to complete absence of mature melanocytes with others. In the trunk region of wild-type embryos, Mitf-expressing cells that coexpressed the melanoblast marker Dct and the tyrosine kinase receptor Kit were ...

The mouse microphthalmia (Mitf) gene encodes a basic-helix-loop-helix-zipper transcription factor whose mutations are associated with abnormalities in neuroepithelial and neural crest-derived melanocytes. In wild type embryos, Mitf expression in neuropithelium and neural crest precedes that of the melanoblast marker Dct, is then co-expressed with Dct, and gradually fades away except in cells in...

The Microphthalmia-associated transcription factor (MITF) is an important regulator of cell-type specific functions in melanocytic cells. MITF is essential for the survival of pigmented cells, but whereas high levels of MITF drive melanocyte differentiation, lower levels are required to permit proliferation and survival of melanoma cells. MITF is phosphorylated by ERK, and this stimulates its a...

BACKGROUND Congestive heart failure (CHF) is a significant health care burden in developed countries. However, the molecular events leading from cardiac hypertrophy to CHF are unclear and preventive therapeutic approaches are limited. We have previously described that microphthalmia-associated transcription factor (MITF) is a key regulator of cardiac hypertrophy, but its cardiac targets are sti...

The mouse mi locus encodes a basic-helix-loop-helix-leucine zipper-type transcription factor, microphthalmia transcription factor (MITF). Mice of mi/mi genotype express a mutant form of MITF (mi-MITF), whereas mice of tg/tg genotype have a transgene in the 5' flanking region of the mi gene and do not express MITF. Although the mi/mi mouse is deficient in natural killer (NK) activity, it was fou...

During vertebrate eye development, the transcription factor MITF plays central roles in neuroepithelial domain specification and differentiation of the retinal pigment epithelium. MITF is not a single protein but represents a family of isoforms generated from a common gene by alternative promoter/exon use. To address the question of the role and regulation of these isoforms, we first determined...