Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation

Abstract

Cells damaged by environmental insults have to be repaired or eliminated to ensure tissue homeostasis in metazoans. Recent studies suggest that the balance between cell survival signals and pro-apoptotic stimuli controls the decision between cell repair and death. How these competing signals are integrated and interpreted to achieve accurate control over cell fate in vivo is incompletely understood. Here, we show that the Forkhead Box O transcription factor Foxo and the AP-1 transcription factor DFos are required downstream of Jun-N-terminal kinase signaling for the apoptotic response to UV-induced DNA damage in the developing Drosophila retina. Both transcription factors regulate the pro-apoptotic gene hid. Our results indicate that UV-induced apoptosis is repressed by receptor tyrosine kinase-mediated inactivation of Foxo. These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo.

A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila

“…As dp53 and the JNK pathway appear to be key factors in apoptosis, we first examined their ability to induce proapoptotic genes. As expected from previous work, 11,12,20,25 both dp53 and JNK can activate hid and rpr: in sal4dp53 and in sal4 hep ACT discs (where hep ACT provides constitutive activity of the JNK pathway 26 ), the two proapoptotic genes become expressed in the spalt (sal) domain (Figures 1d-g). The induction also occurs in discs of the null allelic combination dronc I24 /dronc I29 (hereafter referred to as dronc À ), indicating that hid and rpr induction by dp53 and JNK is not mediated by a feedback loop (Figures 1h-k).…”

Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells

“…survival signals results in FOXO translocating to the nucleus from the cytoplasm and inducing apoptosis (19,20). Recently, it was reported that low levels of insulin-like growth factor 1 in human blood induced midgut FOXO activation, resulting in increased Anopheles stephensi lifespan (21).…”

“…JNK activates the transcription factors forkhead box O (FOXO) and Fos, that in turn activate Hid expression (19). FOXO is part of a family of transcription factors that is phosphorylated by Akt or IKK in response to signals promoting survival (19).…”

Cell death: what can we learn from flies? Editorial for the special review issue on Drosophila apoptosis

“…In Drosophila, JNK has been implicated in development in dorsal and thorax closure, imaginal disc eversion, planar cell polarity. It is also involved in the immune response, response to cellular damage, wound healing, longevity and apoptosis (for reviews covering these topics see [50][51][52] Initial studies have shown that the activation of the Tumor Necrosis Factor/Tumor Necrosis Factor Receptor (TNF/TNFR) system in flies (Eiger/Wengen) induces JNKdependent cell death in stress situations but is not required for developmental apoptosis [53][54][55]. However, a recent study showed that JNK signaling contributed to morphogenetic apoptosis during normal development.…”