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STAT3β does not interfere with granulocyte colony-stimulating factor-induced neutrophilic differentiation
journal contributionposted on 2000-01-01, 00:00 authored by J P De Koning, Alister WardAlister Ward, E Caldenhoven, R P De Groot, B Löwenberg, I P Touw
Introduction: Activation of the signal transducer and activator of transcription protein STAT3 is a crucial step in granulocyte colony-stimulating factor (G-CSF)-mediated cell cycle exit and subsequent neutrophilic differentiation of myeloid precursor cells. We have recently demonstrated that this is mediated, at least in part, by upregulation of the cyclin-dependent kinase inhibitor p27Kip1. The splice variant STAT3β, that lacks a C-terminal serine residue implicated in the transcriptional activity of STAT3, has been shown to inhibit STAT3-mediated transcription in certain situations. STAT3β is known to be expressed in hematopoietic cells, but its role in controlling the balance between proliferation and differentiation has not been established. Materials and methods: We ectopically introduced STAT3β in differentiation-competent 32D cell transfectants expressing human wild type (WT) G-CSF receptors and studied the consequences for G-CSF-mediated responses. Results: Overexpression of STAT3β did not alter the kinetics of G-CSF-mediated neutrophilic differentiation or p27 induction in 32D/G-CSF-R WT cells. In addition, we found that p27Kip1 promoter activity was not inhibited by STAT3β, while inhibition of p27 transactivation by a dominant-negative STAT3 mutant could in fact be alleviated by coexpression of the β form. Conclusion: These findings argue against a role of STAT3β as a negative regulator of G-CSF-induced expression of p27 and myeloid differentiation.
Pagination220 - 225
Publication classificationCN.1 Other journal article
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Alternative SplicingAnimalsCell Cycle ProteinsCell DifferentiationCell LineCyclin-Dependent Kinase Inhibitor p27DNA-Binding ProteinsGene Expression RegulationGranulocyte Colony-Stimulating FactorHeLa CellsHumansInterleukin-3MiceMyeloid CellsNeutrophilsProtein IsoformsReceptors, Granulocyte Colony-Stimulating FactorSTAT3 Transcription FactorSignal TransductionTrans-ActivatorsTranscriptional ActivationTransfectionTumor Suppressor Proteins