Your browser doesn't support javascript.
loading
The SCL/TAL1 Transcription Factor Represses the Stress Protein DDiT4/REDD1 in Human Hematopoietic Stem/Progenitor Cells.
Benyoucef, Aissa; Calvo, Julien; Renou, Laurent; Arcangeli, Marie-Laure; van den Heuvel, Anita; Amsellem, Sophie; Mehrpour, Maryam; Larghero, Jerome; Soler, Eric; Naguibneva, Irina; Pflumio, Francoise.
Afiliação
  • Benyoucef A; CEA, DSV-IRCM-SCSR-LSHL, UMR 967, équipe labellisée Ligue Nationale contre le Cancer, Fontenay-aux-Roses, Paris, France.
  • Calvo J; INSERM, U967, Fontenay-aux-Roses, Paris, France.
  • Renou L; Université Paris Diderot, UMR 967, Fontenay-aux-Roses, Paris, France.
  • Arcangeli ML; Université Paris-Sud, UMR 967, Fontenay-aux-Roses, Paris, France.
  • van den Heuvel A; CEA, DSV-IRCM-SCSR-LSHL, UMR 967, équipe labellisée Ligue Nationale contre le Cancer, Fontenay-aux-Roses, Paris, France.
  • Amsellem S; INSERM, U967, Fontenay-aux-Roses, Paris, France.
  • Mehrpour M; Université Paris Diderot, UMR 967, Fontenay-aux-Roses, Paris, France.
  • Larghero J; Université Paris-Sud, UMR 967, Fontenay-aux-Roses, Paris, France.
  • Soler E; CEA, DSV-IRCM-SCSR-LSHL, UMR 967, équipe labellisée Ligue Nationale contre le Cancer, Fontenay-aux-Roses, Paris, France.
  • Naguibneva I; INSERM, U967, Fontenay-aux-Roses, Paris, France.
  • Pflumio F; Université Paris Diderot, UMR 967, Fontenay-aux-Roses, Paris, France.
Stem Cells ; 33(7): 2268-79, 2015 Jul.
Article em En | MEDLINE | ID: mdl-25858676
Hematopoietic stem/progenitor cells (HSPCs) are regulated through numerous molecular mechanisms that have not been interconnected. The transcription factor stem cell leukemia/T-cell acute leukemia 1 (TAL1) controls human HSPC but its mechanism of action is not clarified. In this study, we show that knockdown (KD) or short-term conditional over-expression (OE) of TAL1 in human HSPC ex vivo, respectively, blocks and maintains hematopoietic potentials, affecting proliferation of human HSPC. Comparative gene expression analyses of TAL1/KD and TAL1/OE human HSPC revealed modifications of cell cycle regulators as well as previously described TAL1 target genes. Interestingly an inverse correlation between TAL1 and DNA damage-induced transcript 4 (DDiT4/REDD1), an inhibitor of the mammalian target of rapamycin (mTOR) pathway, is uncovered. Low phosphorylation levels of mTOR target proteins in TAL1/KD HSPC confirmed an interplay between mTOR pathway and TAL1 in correlation with TAL1-mediated effects of HSPC proliferation. Finally chromatin immunoprecipitation experiments performed in human HSPC showed that DDiT4 is a direct TAL1 target gene. Functional analyses showed that TAL1 represses DDiT4 expression in HSPCs. These results pinpoint DDiT4/REDD1 as a novel target gene regulated by TAL1 in human HSPC and establish for the first time a link between TAL1 and the mTOR pathway in human early hematopoietic cells. Stem Cells 2015;33:2268-2279.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco / Fatores de Transcrição / Células-Tronco Hematopoéticas / Proteínas Proto-Oncogênicas / Peptídeos e Proteínas de Sinalização Intracelular / Fatores de Transcrição Hélice-Alça-Hélice Básicos / Proteínas de Choque Térmico Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco / Fatores de Transcrição / Células-Tronco Hematopoéticas / Proteínas Proto-Oncogênicas / Peptídeos e Proteínas de Sinalização Intracelular / Fatores de Transcrição Hélice-Alça-Hélice Básicos / Proteínas de Choque Térmico Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article