MYELOID NEOPLASIA KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation
نویسندگان
چکیده
1Pediatric Hematology, Johns Hopkins University, Baltimore, MD; 2Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD; 3Howard Hughes Medical Institute, Baltimore, MD; 4Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; 5Adult Hematology, Johns Hopkins University, Baltimore, MD; 6Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN; and 7Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
منابع مشابه
KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation.
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,...
متن کاملInvolvement of transcription factor encoded by the mi locus in the expression of c-kit receptor tyrosine kinase in cultured mast cells of mice.
The mi locus of mice encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Cultured mast cells of mi/mi genotype (mi/mi CMCs) did not normally respond to stem cell factor (SCF), a ligand for the c-kit receptor tyrosine kinase. The poor response of mi/mi CMCs to SCF was attributed to the deficient expression of c...
متن کاملLoss of epigenetic regulator TET2 and oncogenic KIT regulate myeloid cell transformation via PI3K pathway.
Mutations in KIT and TET2 are associated with myeloid malignancies. We show that loss of TET2-induced PI3K activation and -increased proliferation is rescued by targeting the p110α/δ subunits of PI3K. RNA-Seq revealed a hyperactive c-Myc signature in Tet2-/- cells, which is normalized by inhibiting PI3K signaling. Loss of TET2 impairs the maturation of myeloid lineage-derived mast cells by dysr...
متن کاملLAT-derived microRNAs in HSV-1 target SMAD3 and SMAD4 in TGF-β/Smad signaling pathway
Background: During its latent infection, HSV-1 produces only a miRNA precursor called LAT, which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs could target cellular mRNAs. One of the key cell signaling pathways that can be affected by HSV-1 is the TGF-β/Smad pathway. Herein, we investigated the potential role of the LAT as well as three LAT-derived miRNAs ...
متن کاملThe PI3K pathway drives the maturation of mast cells via microphthalmia transcription factor.
Mast cell maturation is poorly understood. We show that enhanced PI3K activation results in accelerated maturation of mast cells by inducing the expression of microphthalmia transcription factor (Mitf). Conversely, loss of PI3K activation reduces the maturation of mast cells by inhibiting the activation of AKT, leading to reduced Mitf but enhanced Gata-2 expression and accumulation of Gr1(+)Mac...
متن کامل