Control of erythroid cell production via caspase-mediated cleavage of transcription factor SCL/Tal-1

Ruggero De Maria Marchiano, A. Zeuner, A. Eramo, U. Testa, N. Felli, E. Pelosi, G. Mariani, S. M. Srinivasula, E. S. Alnemri, G. Condorelli, C. Peschle

Risultato della ricerca: Contributo in rivistaArticolo in rivista

41 Citazioni (Scopus)

Abstract

SCL/Tal-1 is a helix-loop-helix (HLH) transcription factor required for blood cell development, whose abnormal expression is responsible for induction of T-cell acute lymphoblastic leukemia. We show here that SCL/Tal-1 is a key target of caspases in developing erythroblasts. SCL/Tal-1 degradation occurred rapidly after caspase activation and preceded the cleavage of the major erythroid transcription factor GATA-1. Expression of a caspase-resistant SCL/Tal-1 in erythroid progenitors was able to prevent amplification of caspase activation, GATA-1 degradation and impaired erythropoiesis induced by growth factor deprivation or death receptor triggering. The potent proerythropoietic activity of uncleavable SCL/Tal-1 was clearly evident in the absence of erythropoietin, a condition that did not allow survival of normal erythroid cells or expansion of erythroblasts expressing caspase-resistant GATA-1. In the absence of erythropoietin, cells expressing caspase-resistant SCL/Tal-1 maintain high levels of Bcl-XL, which inhibits amplification of the caspase cascade and mediates protection from apoptosis. Thus, SCL/TAL-1 is a survival factor for erythroid cells, whereas caspase-mediated cleavage of SCL/Tal-1 results in amplification of caspase activation, GATA-1 degradation and impaired erythropoiesis.
Lingua originaleEnglish
pagine (da-a)905-913
Numero di pagine9
RivistaCell Death and Differentiation
Volume10
DOI
Stato di pubblicazionePubblicato - 2003

Keywords

  • Amino Acid Chloromethyl Ketones
  • Antibodies
  • Apoptosis
  • B-Lymphocytes
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Western
  • CD95 (APO-1
  • Caspase 3
  • Caspase 7
  • Caspase 8
  • Caspases
  • Cell Biology
  • Cell Division
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Down-Regulation
  • E proteins
  • Enzyme Precursors
  • Erythroblasts
  • Erythroid-Specific DNA-Binding Factors
  • Erythropoiesis
  • Erythropoietin
  • Fas) stem cell leukemia
  • GATA1 Transcription Factor
  • GATA2 Transcription Factor
  • Gene Expression Regulation
  • Green Fluorescent Proteins
  • Helix-Loop-Helix Motifs
  • Hematopoiesis
  • Humans
  • Luminescent Proteins
  • Microscopy, Fluorescence
  • Molecular Biology
  • Mutagenesis, Site-Directed
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors
  • Transcription factors
  • bcl-X Protein
  • fas Receptor

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