1. Academic Validation
  2. Phosphothreonine Lyase Promotes p65 Degradation in a Mitogen-Activated Protein Kinase/Mitogen- and Stress-Activated Protein Kinase 1-Dependent Manner

Phosphothreonine Lyase Promotes p65 Degradation in a Mitogen-Activated Protein Kinase/Mitogen- and Stress-Activated Protein Kinase 1-Dependent Manner

  • Infect Immun. 2018 Dec 19;87(1):e00508-18. doi: 10.1128/IAI.00508-18.
Mingyu Hou 1 Wenhui Wang 1 Feizi Hu 1 Yuanxing Zhang 1 2 3 Dahai Yang 1 2 Qin Liu 4 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
  • 2 Shanghai Engineering Research Center of Marine Cultured Animal Vaccines, Shanghai, China.
  • 3 Shanghai Collaborative Innovation Center for Biomanufacturing, Shanghai, China.
  • 4 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China qinliu@ecust.edu.cn.
Abstract

Bacterial phosphothreonine lyases have been identified to be type III secretion system (T3SS) effectors that irreversibly dephosphorylate host mitogen-activated protein kinase (MAPK) signaling to promote Infection. However, the effects of phosphothreonine lyase on nuclear factor κB (NF-κB) signaling remain largely unknown. In this study, we detected significant phosphothreonine lyase-dependent p65 degradation during Edwardsiella piscicida Infection in macrophages, and this degradative effect was blocked by the protease inhibitor MG132. Further analysis revealed that phosphothreonine lyase promotes the dephosphorylation and ubiquitination of p65 by inhibiting the phosphorylation of mitogen- and stress-activated protein kinase-1 (MSK1) and by inhibiting the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2), p38α, and c-Jun N-terminal kinase (JNK). Moreover, we revealed that the catalytic active site of phosphothreonine lyase plays a critical role in regulating the MAPK-MSK1-p65 signaling axis. Collectively, the mechanism described here expands our understanding of the pathogenic effector in not only regulating MAPK signaling but also regulating p65. These findings uncover a new mechanism by which pathogenic bacteria overcome host innate immunity to promote pathogenesis.

Keywords

MAPKs; MSK1; p65 degradation; phosphothreonine lyase.

Figures
Products