title: 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.affiliation: Department of Ophthalmology, University Hospital Zurich, Switzerland. Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Iseli
authors.forename: Alexander
authors.initials: A
authors.lastname: Fleischmann
authors.forename: Farhad
authors.initials: F
authors.lastname: Hafezi
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Remé
mesh_terms: D000818:Animals; D017209:Apoptosis; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D000099169:Fos-Related Antigen 1
chemical_list: D003907:Dexamethasone; D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1