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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2008

AutorInnen: Kerenyi, MA; Grebien, F; Gehart, H; Schifrer, M; Artaker, M; Kovacic, B; Beug, H; Moriggl, R; Müllner, EW

Titel: Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1.

Quelle: Blood. 2008; 112(9):3878-3888



Autor/innen der Vetmeduni Vienna:

Grebien Florian

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!


Abstract:
Erythropoiesis strictly depends on signal transduction through the erythropoietin receptor (EpoR)-Janus kinase 2 (Jak2)-signal transducer and activator of transcription 5 (Stat5) axis, regulating proliferation, differentiation, and survival. The exact role of the transcription factor Stat5 in erythropoiesis remained puzzling, however, since the first Stat5-deficient mice carried a hypomorphic Stat5 allele, impeding full phenotypical analysis. Using mice completely lacking Stat5--displaying early lethality--we demonstrate that these animals suffer from microcytic anemia due to reduced expression of the antiapoptotic proteins Bcl-x(L) and Mcl-1 followed by enhanced apoptosis. Moreover, transferrin receptor-1 (TfR-1) cell surface levels on erythroid cells were decreased more than 2-fold on erythroid cells of Stat5(-/-) animals. This reduction could be attributed to reduced transcription of TfR-1 mRNA and iron regulatory protein 2 (IRP-2), the major translational regulator of TfR-1 mRNA stability in erythroid cells. Both genes were demonstrated to be direct transcriptional targets of Stat5. This establishes an unexpected mechanistic link between EpoR/Jak/Stat signaling and iron metabolism, processes absolutely essential for erythropoiesis and life.

Keywords Pubmed: Anemia, Iron-Deficiency/genetics
Anemia, Iron-Deficiency/metabolism
Anemia, Iron-Deficiency/pathology
Animals
Apoptosis
Biological Transport, Active
Embryo Loss
Erythroid Cells/metabolism*
Erythroid Cells/pathology
Female
Iron/deficiency
Iron/metabolism*
Iron Regulatory Protein 2/metabolism*
Liver/embryology
Liver/metabolism
Liver/pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cell Leukemia Sequence 1 Protein
Pregnancy
Proto-Oncogene Proteins c-bcl-2/metabolism
RNA, Messenger/genetics
RNA, Messenger/metabolism
Receptors, Transferrin/metabolism*
STAT5 Transcription Factor/deficiency
STAT5 Transcription Factor/genetics
STAT5 Transcription Factor/metabolism*


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