2. Academic Validation
  3. EGLN1 prolyl hydroxylation of hypoxia-induced transcription factor HIF1α is repressed by SET7-catalyzed lysine methylation

EGLN1 prolyl hydroxylation of hypoxia-induced transcription factor HIF1α is repressed by SET7-catalyzed lysine methylation

  • J Biol Chem. 2022 Jun;298(6):101961. doi: 10.1016/j.jbc.2022.101961.
Jinhua Tang 1,  Hongyan Deng 2,  Zixuan Wang 1,  Huangyuan Zha 3,  Qian Liao 1,  Chunchun Zhu 1,  Xiaoyun Chen 1,  Xueyi Sun 1,  Shuke Jia 1,  Gang Ouyang 1,  Xing Liu 4,  Wuhan Xiao 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
  • 2 College of Life Science, Wuhan University, Wuhan, China.
  • 3 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
  • 4 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China; The Innovation of Seed Design, Chinese Academy of Sciences, Wuhan, China. Electronic address: liuxing@ihb.ac.cn.
  • 5 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China; The Innovation of Seed Design, Chinese Academy of Sciences, Wuhan, China; Hubei Hongshan Laboratory, Wuhan, China. Electronic address: w-xiao@ihb.ac.cn.
PMID: 35452683 DOI: 10.1016/j.jbc.2022.101961
Abstract

Egg-laying defective nine 1 (EGLN1) functions as an oxygen sensor to catalyze prolyl hydroxylation of the transcription factor hypoxia-inducible factor-1 α under normoxia conditions, leading to its proteasomal degradation. Thus, EGLN1 plays a central role in the hypoxia-inducible factor-mediated hypoxia signaling pathway; however, the posttranslational modifications that control EGLN1 function remain largely unknown. Here, we identified that a lysine monomethylase, SET7, catalyzes EGLN1 methylation on lysine 297, resulting in the repression of EGLN1 activity in catalyzing prolyl hydroxylation of hypoxia-inducible factor-1 α. Notably, we demonstrate that the methylation mimic mutant of EGLN1 loses the capability to suppress the hypoxia signaling pathway, leading to the enhancement of cell proliferation and the oxygen consumption rate. Collectively, our data identify a novel modification of EGLN1 that is critical for inhibiting its enzymatic activity and which may benefit cellular adaptation to conditions of hypoxia.

Keywords

EGLN1; SET7; gene expression; hypoxia signaling; methylation.

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