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 originale | Inglese |
---|---|
pagine (da-a) | 905-913 |
Numero di pagine | 9 |
Rivista | Cell Death and Differentiation |
Volume | 10 |
DOI | |
Stato di pubblicazione | Pubblicato - 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