ORCID Profile
0000-0003-4530-6460
Current Organisation
Graduate School of Medical Sciences, Kyushu University
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-05-2007
Abstract: Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell–instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage.
Publisher: eLife Sciences Publications, Ltd
Date: 29-05-2017
DOI: 10.7554/ELIFE.24767
Abstract: Heme is required for survival of all cells, and in most eukaryotes, is produced through a series of eight enzymatic reactions. Although heme production is critical for many cellular processes, how it is coupled to cellular differentiation is unknown. Here, using zebrafish, murine, and human models, we show that erythropoietin (EPO) signaling, together with the GATA1 transcriptional target, AKAP10 , regulates heme biosynthesis during erythropoiesis at the outer mitochondrial membrane. This integrated pathway culminates with the direct phosphorylation of the crucial heme biosynthetic enzyme, ferrochelatase (FECH) by protein kinase A (PKA). Biochemical, pharmacological, and genetic inhibition of this signaling pathway result in a block in hemoglobin production and concomitant intracellular accumulation of protoporphyrin intermediates. Broadly, our results implicate aberrant PKA signaling in the pathogenesis of hematologic diseases. We propose a unifying model in which the erythroid transcriptional program works in concert with post-translational mechanisms to regulate heme metabolism during normal development.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2005
DOI: 10.1038/NATURE03203
Abstract: Aberrant transcriptional repression through chromatin remodelling and histone deacetylation has been postulated to represent a driving force underlying tumorigenesis because histone deacetylase inhibitors have been found to be effective in cancer treatment. However, the molecular mechanisms by which transcriptional derepression would be linked to tumour suppression are poorly understood. Here we identify the transcriptional repressor Pokemon (encoded by the Zbtb7 gene) as a critical factor in oncogenesis. Mouse embryonic fibroblasts lacking Zbtb7 are completely refractory to oncogene-mediated cellular transformation. Conversely, Pokemon overexpression leads to overt oncogenic transformation both in vitro and in vivo in transgenic mice. Pokemon can specifically repress the transcription of the tumour suppressor gene ARF through direct binding. We find that Pokemon is aberrantly overexpressed in human cancers and that its expression levels predict biological behaviour and clinical outcome. Pokemon's critical role in cellular transformation makes it an attractive target for therapeutic intervention.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-01-2016
Abstract: Mutation of adult-type globin genes causes sickle cell disease and thalassemia. Although treating these hemoglobinopathies with gene therapy is possible, there is a pressing need for pharmacologic approaches to treat general patient populations. One promising approach is to reactivate repressed expression of fetal-type hemoglobin (HbF) in adult erythroid cells. Masuda et al. reveal a molecular mechanism governing HbF repression as mediated by the LRF/ZBTB7A transcription factor. The study may encourage the development of new HbF reactivation therapies for hemoglobinopathies. Science , this issue p. 285
Location: Japan
Location: United States of America
Location: United States of America
No related grants have been discovered for Takahiro Maeda.