Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors

  1. Stephan P. Persengiev,
  2. Laxminarayana R. Devireddy, and
  3. Michael R. Green1
  1. Howard Hughes Medical Institute and Programs in Molecular Medicine and Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

Abstract

The mammalian ATF/CREB family of transcription factors comprises a large group of basic-region leucine zipper (bZIP) proteins whose members mediate diverse transcriptional regulatory functions. Here we report that expression of a specific mouse ATF gene,ATFx, is down-regulated in a variety of cells undergoing apoptosis following growth factor deprivation. When stably expressed in an interleukin 3 (IL-3)-dependent cell line, ATFx suppresses apoptosis resulting from cytokine deprivation. Conversely, a dominant-negative ATFx mutant induces apoptosis of cells cultured in the presence of growth factors. We also show that 24p3, a secreted lipocalin that induces apoptosis when added to hematopoietic cells, represses ATFx expression. However, constitutive expression ofATFx renders cells resistant to 24p3-mediated apoptosis. Collectively, our results indicate that ATFx is an anti-apoptotic factor, a novel role for an ATF protein.

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Footnotes

  • 1 Corresponding author.

  • E-MAIL michael.green{at}umassmed.edu; FAX (508) 856-5473.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.992202.

    • Received March 18, 2002.
    • Accepted May 22, 2002.
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