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Regulator of differentiation 1 (ROD1) binds to the amphipathic C-terminal peptide of thrombospondin-4 and is involved in its mitogenic activity.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2009 Sep; Vol. 220 (3), pp. 672-9. - Publication Year :
- 2009
-
Abstract
- The matrix protein thrombospondin-4 has an acidic amphipathic C-terminal peptide (C21) which stimulates erythroid cell proliferation. Here we show that C21 stimulates red cell formation in anemic mice in vivo. In vitro experiments indicated that the peptide-mediated increase of erythroid colony formation in cultures of human CD34+ hematopoietic progenitor cells was possible only under continuous presence of erythropoietin. In the absence of this cytokine, C21 stimulated exclusively myeloid colony formation. Therefore, the peptide is not a specific erythroid differentiation factor. In fact, it is mitogenic in non-erythroid cells, such as skin fibroblasts and kidney epithelial cells. In erythroleukemic TF-1 cells, it actually decreased the production of the erythroid differentiation marker glycophorin A. C21-affinity chromatography revealed regulator of differentiation 1 (ROD1) as a major C21-binding protein. ROD1 is the hematopoietic cell paralog of polypyrimidine tract binding proteins (PTBs), RNA splice regulators which regulate differentiation by repressing tissue-specific exons. ROD1 binding to C21 was strongly inhibited by synthetic RNAs in the order poly A > poly U > poly G = poly C and was weakly inhibited by a synthetic phosphorylated peptide mimicking the C-terminal domain of RNA polymerase II. Cellular overexpression or knockdown experiments of ROD1 suggest a role for this protein in the mitogenic activity of C21. Since the nuclear proteins ROD1 and PTBs regulate differentiation at a posttranscriptional level and there is a fast nuclear uptake of C21, we put forward the idea that the peptide is internalized, goes to the nucleus and maintains cells in a proliferative state by supporting ROD1-mediated inhibition of differentiation.
- Subjects :
- Active Transport, Cell Nucleus
Anemia chemically induced
Animals
Binding Sites
Cells, Cultured
Disease Models, Animal
Epithelial Cells metabolism
Erythropoietin metabolism
Fibroblasts metabolism
Glycophorins metabolism
Humans
Kidney metabolism
Leukemia, Erythroblastic, Acute metabolism
Leukemia, Erythroblastic, Acute pathology
Male
Mice
Mice, Inbred C57BL
Peptide Fragments chemistry
Polypyrimidine Tract-Binding Protein metabolism
Protein Structure, Tertiary
RNA Interference
RNA-Binding Proteins genetics
Recombinant Proteins metabolism
Skin metabolism
Thrombospondins chemistry
Time Factors
Transduction, Genetic
Zidovudine
Anemia blood
Cell Proliferation
Erythroid Precursor Cells metabolism
Erythropoiesis
Peptide Fragments metabolism
RNA-Binding Proteins metabolism
Thrombospondins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 220
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 19441079
- Full Text :
- https://doi.org/10.1002/jcp.21817