2. Academic Validation
  3. Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways

Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways

  • Cell Death Dis. 2017 May 4;8(5):e2763. doi: 10.1038/cddis.2017.102.
Jing Zhong 1 2,  Huihui Wang 3,  Wankun Chen 1 2,  Zhirong Sun 1 2,  Jiawei Chen 1 2,  Yajun Xu 1 2,  Meilin Weng 1 2,  Qiqing Shi 4,  Duan Ma 5,  Changhong Miao 1 2 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 3 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
  • 4 Department of Anesthesiology, Children's Hospital of Fudan University, Shanghai, China.
  • 5 Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
PMID: 28471450 DOI: 10.1038/cddis.2017.102
Abstract

Sepsis is a systemic inflammation caused by Infection. The balance between M1-M2 macrophage polarization has an essential role in the pathogenesis of sepsis. However, the exact mechanism underlying macrophage polarization is unclear. We previously showed that levels of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) were significantly elevated in septic patients compared with those in nonseptic patients, and involved in the activation of Toll-like Receptor (TLR) 2/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB pathway. In the present study, we explored whether MFHAS1 was involved in macrophage polarization and determined the effect of MFHAS1 on inflammation. We performed in vitro pulldown assays and in vivo co-immunoprecipitation assays and found that E3 ubiquitin ligase praja2 could directly bind to MFHAS1. In situ immunostaining analysis confirmed the colocalization of endogenous praja2 with MFHAS1. We first reported that praja2 promotes the accumulation of ubiquitylated MFHAS1 but does not degrade it. Moreover, our results indicate that MFHAS1 ubiquitylation by praja2 positively regulates TLR2-mediated JNK/p38 pathway and promotes M1 macrophage polarization, M2 to M1 macrophage transformation and inflammation.

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