Pyruvate Kinase M2 Promotes the Activation of Dendritic Cells by Enhancing IL-12p35 Expression
| Autor: | Jiaxin Dong, Yunpeng Feng, Yunlong Li, Miaomiao Tian, Hengyao Shu, Xin Jin, Fengqi Hao, Min Wei, Wenxia Zhang, Jia Liu, Yang Wang |
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| Rok vydání: | 2020 |
| Předmět: |
K433 acetylation
0301 basic medicine dendritic cell Cellular differentiation Pyruvate Kinase PKM2 Interleukin-12 Subunit p35 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Humans Glycolysis lcsh:QH301-705.5 Fatty acid synthesis Dendritic Cells Dendritic cell Acquired immune system Cell biology 030104 developmental biology lcsh:Biology (General) chemistry IL-12 JNK 030217 neurology & neurosurgery Pyruvate kinase |
| Zdroj: | Cell Reports, Vol 31, Iss 8, Pp-(2020) |
| ISSN: | 2211-1247 |
| Popis: | Summary: Dendritic cells (DCs) play a central role in both innate and adaptive immunity. Emerging evidence has demonstrated metabolic reprogramming during DC activation. However, how DC activation is linked with metabolic reprogramming remains unclear. Here we show that pyruvate kinase M2 (PKM2), the rate-limiting enzyme in the last step of glycolysis, is critical for LPS-induced DC activation. Upon DC activation, JNK signaling stimulated p300 association with PKM2 for the acetylation of lysine 433, a classic posttranslational modification critical for PKM2 destabilization and nuclear re-localization. Subsequently, nuclear PKM2 partnered with c-Rel to enhance Il12p35 expression, which is important for Th1 cell differentiation. Meanwhile, decreased enzymatic activity of PKM2 due to detetramerization facilitated glycolysis and fatty acid synthesis, helping DCs meet their need for biomacromolecules. Together, we provide evidence for metabolic control of DC activation and offer insights into aberrant immune responses due to dysregulated Th1 functions. |
| Databáze: | OpenAIRE |
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