Fra-1 substitutes for c-Fos in AP-1-mediated signal transduction in retinal apoptosis.

Abstract

Lack of the AP-1 member c-Fos protects photoreceptors against light-induced apoptosis, a model for retinal degeneration. In mice, light damage increases the activity of the transcription factor AP-1, while pharmacological suppression of AP-1 prevents apoptosis, suggesting the involvement of pro-apoptotic AP-1 target genes. Recently, however, it was shown that photoreceptors expressing Fra-1 in place of c-Fos (Fos (Fosl1/Fosl1) ) are apoptosis competent despite the lack of transactivation domains in Fra-1. Here, we show that morphological features of light-induced apoptosis were indistinguishable in Fos (Fosl1/Fosl1) and wild-type mice. Furthermore, light exposure comparably increased AP-1 activity in both genotypes. Opposite to wild-type mice, Fra-1, but not c-Fos, was detectable in AP-1 complexes of Fos (Fosl1/Fosl1) mice. Importantly, AP-1 responsiveness for glucocorticoid receptor-mediated inhibition was preserved in Fos (Fosl1/Fosl1) mice. Thus, Fra-1 takes over for c-Fos in pro- and anti-apoptotic signal transduction. As Fra-1 lacks transactivation domains, AP-1 may not induce, but rather suppress genes in retinal light damage.

• Authors: Andreas Wenzel, Hans Peter Iseli, Alexander Fleischmann, Farhad Hafezi, Christian Grimm, Erwin F Wagner, Charlotte E Remé
• Journal: Journal of neurochemistry (J Neurochem) Vol. 80 Issue 6 Pg. 1089-94 (Mar 2002) ISSN: 0022-3042 [Print] England
• PMID: 11953459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Proto-Oncogene Proteins c-fos
• Receptors, Glucocorticoid
• Transcription Factor AP-1
• fos-related antigen 1
• Dexamethasone

Topics

• Animals
• Apoptosis
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Glucocorticoids (pharmacology)
• In Situ Nick-End Labeling
• Light (adverse effects)
• Mice
• Mice, Knockout
• Proto-Oncogene Proteins c-fos (deficiency, genetics, metabolism)
• Receptors, Glucocorticoid (metabolism)
• Retina (drug effects, pathology, physiopathology, radiation effects)
• Retinal Degeneration (pathology, physiopathology, prevention & control)
• Signal Transduction
• Transcription Factor AP-1 (metabolism)
• Transcriptional Activation