Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells

Leung, Cindy G.; Xu, Yanfei; Mularski, Bretton; Liu, Hui; Gurbuxani, Sandeep; Crispino, John D.

doi:10.1084/jem.20062395

Cited by 95 publications

(69 citation statements)

References 42 publications

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“…The stimulation of EpoR by Epo binding increases GATA-1 gene expression is a positive feedback loop (Chiba , 1991) and induces GATA-1 phosphorylation and activation (Zhao et al, 2000). In addition, survivin was shown to be required for red blood cell formation (Leung et al, 2007). These observations have two consequences.…”

Section: Discussionmentioning

confidence: 99%

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

et al. 2010

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Expression of survivin, a member of the inhibitor of apoptosis protein family, is elevated in human cancers and considered as a new therapeutic target. Mechanism upregulating survivin expression in tumour cells is poorly understood. In this study, we show that breast cancer patients harbouring a polymorphism G235A in the survivin promoter present a higher level of survivin expression. This polymorphism creates a binding site for the transcription factor GATA-1 inducing a second GATA-1-binding site in survivin promoter. At the mRNA level, GATA-1 was present in breast carcinomas and adjacent normal tissues, whereas the protein was only detected in carcinomas by western blot and immunohistochemistry. Transfection of wild-type and different constitutively active GATA-1 mutants (serine 26, 178 or 310) showed that only phospho-serine 26 GATA-1 was able to increase survivin expression. This increase was higher in G235A than in G235G cell lines. Phospho-serine 26 GATA-1 bound directly survivin promoter, with a stronger interaction in G235A than in G235G polymorphism indicating that both GATA-1-binding sites are functional. These data identify GATA-1 as a key feature in tumour aggressiveness by enhancing survivin expression and delineate its targeting as a possible new therapeutic strategy in breast carcinomas.

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Section: Discussionmentioning

confidence: 99%

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

et al. 2010

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“…As evidence for a functional role of survivin in red blood cell maturation, we observed that a subset of survivin heterozygous mice exhibited a decrease in the percentage of enucleated cells as compared to wildtype littermates. 6 Together, these findings led us to hypothesize that survivin plays a novel role in enucleation of erythroblasts.…”

Section: Introductionmentioning

confidence: 99%

A novel role for survivin in erythroblast enucleation

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundNucleus free red blood cells are unique to mammals. During their terminal stage of differentiation, mammalian erythroblasts exit the cell cycle and enucleate. We previously found that survivin, a member of the chromosomal passenger complex that is required for cytokinesis, is highly expressed in late non-dividing cells. The role of survivin in enucleating erythroblasts is not known. Design and MethodsIn order to identify the role of survivin in these late erythroblasts, we performed proteomic analysis on survivin-bound protein complexes purified from murine erythroleukemia cells. Various molecular and cell biological techniques were used to confirm the presence and function of this novel complex. Furthermore, we used survivin fl/fl mice to study the effect of loss of survivin in enucleating erythroblasts. ResultsWe found that survivin failed to co-localize with its known partners' inner centromere protein or Aurora-B in enucleating erythroblasts but rather exists in a multi-protein complex with epidermal growth factor receptor substrate15 and clathrin, two proteins that mediate endocytic vesicle trafficking. As evidence for a direct role of this latter complex in enucleation, we found that knockdown of the genes reduced the efficiency of enucleation of primary human erythroblasts. We also observed that loss of survivin in murine erythroblasts inhibited enucleation and that survivin-deficient cells harbored smaller cytoplasmic vacuoles. Interestingly, vacuolin-1, a small molecule that induces vacuole fusion, rescued the defective enucleation caused by survivin deficiency. ConclusionsThis study identified a novel role for survivin in erythroblast enucleation through previously unknown protein partners.

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“…Germline deletion of Survivin leads to early embryonic lethality at E3.5 [15]. Tissue-specific knockout of Survivin in thymocytes, neuronal precursors, endothelial cells or haematopoietic progenitors resulted in impaired cell proliferation, cell cycle arrest, mitotic spindle defects or apoptosis, all illustrating a physiological role for survivin in normal cell development [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Perinatal survivin is essential for the establishment of pancreatic beta cell mass in mice

Wang

Schroer

et al. 2009

Diabetologia

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Aims/hypothesis Pancreatic beta cells undergo dynamic remodelling during the perinatal period, with enhanced neogenesis, proliferation and apoptosis observed. The molecular mechanisms responsible for these processes have yet to be elucidated. Survivin is an inhibitor of apoptosis, first described as being exclusively expressed in tumour and embryonic tissues with regulatory functions in mitosis and apoptosis. The aim of the present study was to define the essential physiological role of survivin in the pancreas. Methods The expression profile of survivin was assessed in the mouse pancreas, and we generated a Pdx1 promoterdriven Survivin (also known as Birc5) knockout mouse using the Cre-loxP recombination system to determine the essential physiological function of survivin in the pancreas. Results Survivin is transiently expressed in mouse pancreatic islets during the embryonic and neonatal periods. Targeted deletion of Survivin in the pancreas resulted in a significant decline in beta cell mass throughout the perinatal period, leading to glucose intolerance in the adult. Survivin-deficient islets showed decreased cell proliferation as a result of a delay in cell cycle progression with perturbations in cell cycle proteins. Survivin did not, however, play an essential role in beta cell apoptosis either during the physiological remodelling period or in response to streptozotocin. Islet development, islet architecture, microvasculature and apoptosis were not affected by the absence of survivin in the pancreas. Conclusions/interpretation Survivin expression in the pancreatic islets during the perinatal remodelling period is essential for the establishment of beta cell mass through cell cycle regulation.

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Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells

Cited by 95 publications

References 42 publications

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

A novel role for survivin in erythroblast enucleation

Perinatal survivin is essential for the establishment of pancreatic beta cell mass in mice

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