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

Stephan P Persengiev; Laxminarayana R Devireddy; Michael R Green

doi:10.1101/gad.992202

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

Genes Dev. 2002 Jul 15;16(14):1806-14. doi: 10.1101/gad.992202.

Authors

Stephan P Persengiev¹, Laxminarayana R Devireddy, Michael R Green

Affiliation

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 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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Activating Transcription Factors
Acute-Phase Proteins / metabolism
Acute-Phase Proteins / pharmacology
Animals
Apoptosis*
Carrier Proteins / genetics
Carrier Proteins / physiology*
Cell Cycle
Cell Division
Cell Line
Cell Survival
Cyclic AMP Response Element-Binding Protein
DNA-Binding Proteins*
Down-Regulation
HeLa Cells
Humans
Interleukin-3 / pharmacology
Leucine Zippers / genetics
Leucine Zippers / physiology*
Lipocalin-2
Lipocalins
Mice
Oncogene Proteins / metabolism
Oncogene Proteins / pharmacology
Proto-Oncogene Proteins
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / physiology
Transcription Factors / genetics
Transcription Factors / physiology*

Substances

ATF7 protein, human
Activating Transcription Factors
Acute-Phase Proteins
Carrier Proteins
Cyclic AMP Response Element-Binding Protein
DNA-Binding Proteins
Interleukin-3
LCN2 protein, human
Lipocalin-2
Lipocalins
Oncogene Proteins
Proto-Oncogene Proteins
Recombinant Fusion Proteins
Transcription Factors
Lcn2 protein, mouse