Hematopoiesis controlled by distinct TIF1γ and smad4 branches of the TGFβ pathway Journal Article
| Authors: | He, W.; Dorn, D. C.; Erdjument-Bromage, H.; Tempst, P.; Moore, M. A. S.; Massague, J. |
| Article Title: | Hematopoiesis controlled by distinct TIF1γ and smad4 branches of the TGFβ pathway |
| Abstract: | Tissue homeostasis in mammals relies on powerful cytostatic and differentiation signals delivered by the cytokine TGFβ and relayed within the cell via the activation of Smad transcription factors. Formation of transcription regulatory complexes by the association of Smad4 with receptor-phosphorylated Smads 2 and 3 is a central event in the canonical TGFβ pathway. Here we provide evidence for a branching of this pathway. The ubiquitious nuclear protein Transcriptional Intermediary Factor 1γ (TIF1γ) selectively binds receptor-phosphorylated Smad2/3 in competition with Smad4. Rapid and robust binding of TIF1γ to Smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to TGFβ. In human hematopoietic stem/progenitor cells, where TGFβ inhibits proliferation and stimulates erythroid differentiation, TIF1γ mediates the differentiation response while Smad4 mediates the antiproliferative response with Smad2/3 participating in both responses. Thus, Smad2/3-TIF1γ and Smad2/3-Smad4 function as complementary effector arms in the control of hematopoietic cell fate by the TGFβ/Smad pathway. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; human cell; binding affinity; protein function; cell proliferation; t-lymphocytes; mammalia; mesenchyme cell; nuclear protein; smad2 protein; smad3 protein; transforming growth factor beta; protein binding; cell differentiation; hela cells; cell type; transcription factors; stem cell; erythroid cell; hematopoietic cell; hematopoietic stem cells; epithelium cell; epithelial cells; hematopoiesis; steroid receptor coactivator 1; mesoderm; smad4 protein |
| Journal Title: | Cell |
| Volume: | 125 |
| Issue: | 5 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2006-06-02 |
| Start Page: | 929 |
| End Page: | 941 |
| Language: | English |
| DOI: | 10.1016/j.cell.2006.03.045 |
| PUBMED: | 16751102 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 109" - "Export Date: 4 June 2012" - "CODEN: CELLB" - "Source: Scopus" |
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