PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors

著者: Dongshi Chen, Jingshan Tong, Liheng Yang, Wei Liang, Donna B. Stolz, Jian Yu, Jianke Zhang, Lin Zhang - Proceedings of the National Academy of Sciences, PNAS 2018 被引用: 181

Significance Necroptosis is a regulated form of necrotic cell death that is important in physiology and human diseases. However, the signaling process leading to eventual cell death in necroptosis remains unclear. We show that PUMA , a proapoptotic BH3-only Bcl-2 family member, is induced and plays a role in necroptotic death. PUMA induction enhances necroptotic signaling by promoting the release of mitochondrial DNA and activation of cytosolic DNA sensors. We provide genetic evidence for the functional role of PUMA in necroptosis-mediated developmental defects in mice. Our results demonstrate a previously unknown function of Bcl-2 family proteins and reveal a signal amplification mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF-driven necroptosis in vitro and in vivo.