title: Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway from activin A in hematopoietic cells.
abstract: In the transforming growth factor beta (TGF-beta) superfamily, activin A, TGF-beta1, and bone morphogenic protein 4 (BMP-4) have various effects on hematopoiesis, including early mesodermo-hematogenesis. After these cytokines bind to their respective receptor, a regulatory Smad is phosphorylated and becomes associated with Smad4, the common Smad, and the resulting complex translocates to the nucleus to regulate transcription. DLX1 is the product of a member of the distal-less homeobox gene family, which is known to have important roles in embryogenesis, particularly in craniofacial development, and in GABAergic neurogenesis. DLX1 has been reported to be temporally and spatially coexpressed with BMP-4 during embryogenesis in selected contexts. We report here that, in addition to the previously reported regions/cells, DLX1 is expressed in hematopoietic cells in a lineage-dependent manner and that DLX1 interacts with Smad4 through its homeodomain. We show that it blocks multiple signals from TGF-beta superfamily cytokines such as activin A, TGF-beta1, and BMP-4, including differentiation of a hematopoietic cell line by activin A. Taken together, these data suggest that DLX1 may function as a regulator of multiple signals from TGF-beta superfamily members in broad biological contexts during blood production.
authors.affiliation: Departments of Biology and Human Genetics, Yale University, New Haven, CT 06520-8103, USA. schiba-tky@umin.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takeshita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Imai
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Masuda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Frank H
authors.initials: FH
authors.lastname: Ruddle
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
mesh_terms: D028341:Activins / Q000378:metabolism*; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D006412:Hematopoietic Stem Cells / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D014157:Transcription Factors; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits