Tao Zhang, Daichao Xu, Jianping Liu, Min Wang, Li-Juan Duan, Min Liu, Huyan Meng, Yuan Zhuang, Huibing Wang, Yingnan Wang, Mingming Lv, Zhengyi Zhang, Jia Hu, Linyu Shi, Rui Guo, Xingxing Xie, Hui Liu, Emily Erickson, Yaru Wang, Wenyu Yu, Fabin Dang, Dongxian Guan, Cong Jiang, Xiaoming Dai, Hiroyuki Inuzuka, Peiqiang Yan, Jingchao Wang, Mrigya Babuta, Gewei Lian, Zhenbo Tu, Ji Miao, Gyongyi Szabo, Guo-Hua Fong, Antoine E Karnoub, Yu-Ru Lee, Lifeng Pan, William G Kaelin, Junying Yuan, Wenyi Wei
The prolyl hydroxylation of hypoxia-inducible factor 1α (HIF-1α) mediated by the EGLN-pVHL pathway represents a classic signalling mechanism that mediates cellular adaptation under hypoxia. Here we identify RIPK1, a known regulator of cell death mediated by tumour necrosis factor receptor 1 (TNFR1), as a target of EGLN1-pVHL. Prolyl hydroxylation of RIPK1 mediated by EGLN1 promotes the binding of RIPK1 with pVHL to suppress its activation under normoxic conditions. Prolonged hypoxia promotes the activation of RIPK1 kinase by modulating its proline hydroxylation, independent of the TNFα-TNFR1 pathway...
July 2023: Nature Cell Biology