Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1.
Blood
; 112(9): 3878-88, 2008 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-18694996
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores da Transferrina
/
Proteína 2 Reguladora do Ferro
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Células Eritroides
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Fator de Transcrição STAT5
/
Ferro
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Blood
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Áustria