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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Keerthivasan, Ganesan Wickrema, Amittha Crispino, John D. Gurbuxani, Sandeep Xu, Yanfei |
| Description | Author Affiliation: Gurbuxani S ( The Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Chicago, IL 60637, USA.); |
| Abstract | Although erythroid cells and megakaryocytes arise from a common progenitor, their terminal maturation follows very different paths; erythroid cells undergo cell-cycle exit and enucleation, whereas megakaryocytes continue to progress through the cell cycle but skip late stages of mitosis to become polyploid cells. In our efforts to identify genes that participate in this process, we discovered that survivin, a member of the inhibitor of apoptosis family that also has an essential role in cytokinesis, is differentially expressed during erythroid versus megakaryocyte development. Erythroid cells express survivin throughout their maturation, whereas megakaryocytes express approximately 4-fold lower levels of survivin mRNA and no detectable protein. To investigate the role of survivin in these lineages, we overexpressed or knocked down survivin from mouse bone marrow cells and then examined erythroid and megakaryocyte development. These studies revealed that overexpression of survivin antagonized megakaryocyte growth, maturation, and polyploidization but had no effect on erythroid development. This block in polyploidization was accompanied by increased expression of p21 and decreased expression of megakaryocyte genes such as von Willebrand factor and beta(1)-tubulin. In contrast, a reduction in survivin expression interfered with the formation of erythroid cells but not megakaryocytes. Last, consistent with the requirement for survivin in the survival of proliferating cells, survivin-deficient hematopoietic progenitors failed to give rise to either erythroid or megakaryocytic colonies. Together, these studies show that whereas survivin expression is essential for megakaryocyte and erythroid progenitors, its down-regulation is required for terminal differentiation of megakaryocytes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 32 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Erythrocytes Cytology Gene Expression Regulation Hematopoiesis Physiology Megakaryocytes Microtubule-Associated Proteins Metabolism Neoplasm Proteins Animals Blotting, Western Cells, Cultured Cloning, Molecular Colony-Forming Units Assay Flow Cytometry Green Fluorescent Proteins Inhibitor Of Apoptosis Proteins Mice RNA Interference Reverse Transcriptase Polymerase Chain Reaction Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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