Pontin/Tip49 negatively regulates JNK-mediated cell death in Drosophila

Pontin (Pont), also known as Tip49, encodes a member of the AAA+ ( A TPases A ssociated with Diverse Cellular A ctivities) superfamily and plays pivotal roles in cell proliferation and growth, yet its function in cell death has remained poorly understood. Here we performed a genetic screen for dominant modifiers of Eiger-induced JNK-dependent cell death in Drosophila , and identified Pont as a negative regulator of JNK-mediated cell death. In addition, loss of function of Pont is sufficient to induce cell death and activate the transcription of JNK target gene puc . Furthermore, the epistasis analysis indicates that Pont acts downstream of Hep. Finally, we found that Pont is also required for JNK-mediated thorax development and acts as a negative regulator of JNK phosphorylation. Together, our data suggest that pont encodes a negative component of Egr/JNK signaling pathway in Drosophila through negatively regulating JNK phosphorylation, which provides a novel role of ATPase in Egr-JNK signaling.