Sox6 enhances erythroid differentiation in human erythroid progenitors
Autor: | Rossella Ierardi, Cristina Fugazza, Francesca Bosè, Claudio Cantù, Silvia Piconese, Sergio Ottolenghi, Giuliana Ferrari, Ilaria Alborelli, Letizia Cassinelli, Antonella Ronchi |
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Přispěvatelé: | Cantu', C, Ierardi, R, Alborelli, I, Fugazza, C, Cassinelli, L, Piconese, S, Bosè, F, Ottolenghi, S, Ferrari, G, Ronchi, A, Cantù, C, Ferrari, Giuliana, Ronchi, A. |
Rok vydání: | 2011 |
Předmět: |
Cell type
medicine.medical_treatment Immunology Suppressor of Cytokine Signaling Proteins Antigens CD34 BIO/18 - GENETICA Cell Growth Processes Biology Transfection Models Biological Biochemistry Colony-Forming Units Assay Mice hemic and lymphatic diseases Suppressor of Cytokine Signaling Protein K562 Cell medicine Transcriptional regulation Animals Humans Erythropoiesi Erythropoiesis SOCS3 Transcription factor Cells Cultured Erythroid Precursor Cells Cell Growth Processe Animal Erythroid Precursor Cell Cell Differentiation Cell Biology Hematology Cell biology Cytokine Gene Expression Regulation Suppressor of Cytokine Signaling 3 Protein Cancer research Signal transduction K562 Cells SOXD Transcription Factors Human K562 cells |
Zdroj: | Blood. 117:3669-3679 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood-2010-04-282350 |
Popis: | Sox6 belongs to the Sry (sex-determining region Y)–related high-mobility-group–box family of transcription factors, which control cell-fate specification of many cell types. Here, we explored the role of Sox6 in human erythropoiesis by its overexpression both in the erythroleukemic K562 cell line and in primary erythroid cultures from human cord blood CD34+ cells. Sox6 induced significant erythroid differentiation in both models. K562 cells underwent hemoglobinization and, despite their leukemic origin, died within 9 days after transduction; primary erythroid cultures accelerated their kinetics of erythroid maturation and increased the number of cells that reached the final enucleation step. Searching for direct Sox6 targets, we found SOCS3 (suppressor of cytokine signaling-3), a known mediator of cytokine response. Sox6 was bound in vitro and in vivo to an evolutionarily conserved regulatory SOCS3 element, which induced transcriptional activation. SOCS3 overexpression in K562 cells and in primary erythroid cells recapitulated the growth inhibition induced by Sox6, which demonstrates that SOCS3 is a relevant Sox6 effector. |
Databáze: | OpenAIRE |
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