Yuanyuan Li, Richa B Shah, Samanta Sarti, Alicia L Belcher, Brian J Lee, Andrej Gorbatenko, Francesca Nemati, Honglin Yu, Zoe Stanley, Mahbuba Rahman, Zhengping Shao, Jose M Silva, Shan Zha, Samuel Sidi
Interleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptors (TLRs) and IL-1R in innate immunity. Here, we found that IRAK4 and IRAK1 together inhibited DNA damage-induced cell death independently of TLR or IL-1R signaling. In human cancer cells, IRAK4 was activated downstream of ATR kinase in response to double-strand breaks (DSBs) induced by ionizing radiation (IR). Activated IRAK4 then formed a complex with and activated IRAK1. The formation of this complex required the E3 ubiquitin ligase Pellino1, acting structurally but not catalytically, and the activation of IRAK1 occurred independently of extracellular signaling, intracellular TLRs, and the TLR/IL-1R signaling adaptor MyD88...
December 19, 2023: Science Signaling