Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors.
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 of ATFx 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.
Howard Hughes Medical Institute and Programs in Molecular Medicine and Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Stephan P
SP
Persengiev
Laxminarayana R
LR
Devireddy
Michael R
MR
Green
D051696:Activating Transcription Factors; D000209:Acute-Phase Proteins / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology*; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism / Q000494:pharmacology; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C427752:ATF7 protein, human; D051696:Activating Transcription Factors; D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D007377:Interleukin-3; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C071332:Lcn2 protein, mouse