Dual abnormal effects of mutant MITF encoded by Mi(wh) allele on mouse mast cells: decreased but recognizable transactivation and inhibition of transactivation.
MITF is a basic helix-loop-helix leucine zipper-type transcription factor and is important for development of mast cells. MITF encoded by Mi(wh) allele (Mi(wh)-MITF) was mutated at a single amino acid of basic domain, and possessed a deficient but apparent DNA-binding ability. Here, we characterized the unique effects of Mi(wh)-MITF on the expression of mast cell-related genes. The expression level of mouse mast cell protease (mMCP)-4, -5, and -6 genes in Mi(wh)/Mi(wh) cultured mast cells (CMCs) was intermediate between levels of normal (+/+) CMCs and tg/tg CMCs, which did not express any MITFs. Mi(wh)-MITF appeared to show the positive transactivation effect through the remaining DNA-binding ability. On the other hand, the expression level of tryptophan hydroxylase gene was lower in Mi(wh)/Mi(wh) CMCs than in tg/tg CMCs, suggesting the inhibitory effect of Mi(wh)-MITF on the transactivation. Mi(wh)-MITF possessed dual abnormal effects on transactivation of mast cell-related genes.
Kataoka
Tatsuki R
TR
Department of Pathology, Medical School/Graduate School of Frontier Bioscience, Osaka University Medical School, Yamada-oka 2-2, Suita 565-0871, Japan.
Morii
Eiichi
E
Oboki
Keisuke
K
Jippo
Tomoko
T
Maeyama
Kazutaka
K
Kitamura
Yukihiko
Y
D000483:Alleles; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors