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The leucine zipper region of Myb oncoprotein regulates the commitment of hematopoietic progenitors

Item Type:Article
Title:The leucine zipper region of Myb oncoprotein regulates the commitment of hematopoietic progenitors
Creators Name:Karafiat, V. and Dvorakova, M. and Pajer, P. and Kralova, J. and Horejsi, Z. and Cermak, V. and Bartunek, P. and Zenke, M. and Dvorak, M.
Abstract:The development of blood cells proceeds from pluripotent stem cells through multipotent progenitors into mature elements belonging to at least 8 different lineages. The lineage choice process during which stem cells and progenitors commit to a particular lineage is regulated by a coordinated action of extracellular signals and transcription factors. Molecular mechanisms controlling commitment are largely unknown. Here, the transcription factor v-Myb and its leucine zipper region (LZR) are identified as regulators of the commitment of a common myeloid progenitor and progenitors restricted to the myeloid lineage. It is demonstrated that wild-type v-Myb with the intact LZR directs development of progenitors into the macrophage lineage. Mutations in this region compromise commitment toward myeloid cells and cause v-Myb to also support the development of erythroid cells, thrombocytes, and granulocytes, similar to the c-Myb protein. In agreement with that, the wild-type v-Myb induces high expression of myeloid factors C/EBPβ, PU.1, and Egr-1 in its target cells, whereas SCL, GATA-1, and c-Myb are more abundant in cells expressing the v-Myb LZR mutant. It is proposed that Myb LZR can function as a molecular switch, affecting expression of lineage-specifying transcription factors and directing the development of hematopoietic progenitors into either myeloid or erythroid lineages.
Keywords:Blood Platelets, Cell Differentiation, Chick Embryo, Erythrocytes, Flow Cytometry, Fluorescent Antibody Technique, Gene Deletion, Granulocytes, Hematopoietic Stem Cells, Leucine Zippers, Macrophages, Mutation, Northern Blotting, Oncogene Proteins v-myb, Trans-Activation, Western Blotting, Animals, Chicken
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:98
Number:13
Page Range:3668-3676
Date:1 January 2001
Official Publication:https://doi.org/10.1182/blood.V98.13.3668
PubMed:View item in PubMed

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