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

Gines Morata (1) , Evgeny Shlevkov (1)

1 Centro de Biología Molecular

Programmed cell death (apoptosis) is a conserved process aimed to eliminate unwanted cells. Key molecules are a group of proteases called caspases that cleave vital proteins, which leads to the death of cells. In Drosophila the apoptotic pathway is usually represented as a cascade of events in which an initial stimulus activates one or more of the pro-apoptotic genes (hid, rpr, grim), which in turn activate caspases. In stress-induced apoptosis the dp53 gene and the JNK pathway function upstream in the activation of the pro-apoptotic genes. Here we demonstrate that dp53 and JNK also function downstream of pro-apoptotic genes and the initiator caspase Dronc and that they establish a feedback loop that amplifies the initial apoptotic stimulus. This loop plays a critical role in the apoptotic response because in its absence there is a dramatic decrease in the amount of cell death after a pulse of the pro-apoptotic proteins Hid and Rpr. Thus our results indicate that stress-induced apoptosis in Drosophila is dependant on an amplification loop mediated by dp53 and JNK. Furthermore, they also demonstrate a mechanism of mutual activation of pro-apoptotic genes.

Mots clés: Drosophila; apoptosis; imaginal discs; JNK; p53

Domaines: Biologie cellulaire

Gines Morata, Evgeny Shlevkov. A dp53-JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2011.113⟩. ⟨hal-00675789⟩