Differential requirements for survivin in hematopoietic cell development.

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Title: Differential requirements for survivin in hematopoietic cell development.
Authors: Gurbuxani, Sandeep1,2, Yanfei Xu1, Keerthivasan, Ganesan1, Wickrema, Amittha3, Crispino, John D.1 crispino@uchicago.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 8/9/2005, Vol. 102 Issue 32, p11480-11485. 6p.
Subjects: Hematopoietic growth factors, Growth factors, Colony-stimulating factors (Physiology), Erythropoietin, Thrombopoietin, Bone marrow
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 ≈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 β1-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. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Differential requirements for survivin in hematopoietic cell development.
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  Data: <searchLink fieldCode="DE" term="%22Hematopoietic+growth+factors%22">Hematopoietic growth factors</searchLink><br /><searchLink fieldCode="DE" term="%22Growth+factors%22">Growth factors</searchLink><br /><searchLink fieldCode="DE" term="%22Colony-stimulating+factors+%28Physiology%29%22">Colony-stimulating factors (Physiology)</searchLink><br /><searchLink fieldCode="DE" term="%22Erythropoietin%22">Erythropoietin</searchLink><br /><searchLink fieldCode="DE" term="%22Thrombopoietin%22">Thrombopoietin</searchLink><br /><searchLink fieldCode="DE" term="%22Bone+marrow%22">Bone marrow</searchLink>
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  Data: 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 ≈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 β1-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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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        Value: 10.1073/pnas.0500303102
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      – Code: eng
        Text: English
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        PageCount: 6
        StartPage: 11480
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      – SubjectFull: Hematopoietic growth factors
        Type: general
      – SubjectFull: Growth factors
        Type: general
      – SubjectFull: Colony-stimulating factors (Physiology)
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      – SubjectFull: Erythropoietin
        Type: general
      – SubjectFull: Thrombopoietin
        Type: general
      – SubjectFull: Bone marrow
        Type: general
    Titles:
      – TitleFull: Differential requirements for survivin in hematopoietic cell development.
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            NameFull: Gurbuxani, Sandeep
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            NameFull: Yanfei Xu
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            NameFull: Keerthivasan, Ganesan
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            NameFull: Wickrema, Amittha
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            NameFull: Crispino, John D.
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              Text: 8/9/2005
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              Y: 2005
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