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.