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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)905-913
Number of pages9
JournalCell Death and Differentiation
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

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Keywords

  • CD95 (APO-1
  • E proteins
  • Fas) stem cell leukemia
  • Hematopoiesis
  • Transcription factors

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zeuner, A., Eramo, A., Testa, U., Felli, N., Pelosi, E., Mariani, G., Srinivasula, S. M., Alnemri, E. S., Condorelli, G., Peschle, C., & De Maria, R. (2003). Control of erythroid cell production via caspase-mediated cleavage of transcription factor SCL/Tal-1. Cell Death and Differentiation, 10(8), 905-913. https://doi.org/10.1038/sj.cdd.4401255