A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases

Scientific Reports

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[1] 000000041936877X, grid.5386.8, Boyce Thompson Institute, 14853, Ithaca, New York, USA;000000041936877X, grid.5386.8, Boyce Thompson Institute, 14853, Ithaca, New York, USA;0000 0001 0574 8737, grid.413273.0, College of life sciences and medicine, Zhejiang Sci-Tech University, 310018, Hangzhou, China;000000041936877X, grid.5386.8, Boyce Thompson Institute, 14853, Ithaca, New York, USA;0000 0001 2299 2686, grid.252211.7, Department of Plant Medicals, Andong National University, 36729, Andong, Korea;

DOI  :  10.1038/s41598-019-49234-6

来源: publisher

【 摘 要 】

Salicylic acid (SA) is the major metabolite and active ingredient of aspirin; both compounds reduce pain, fever, and inflammation. Despite over a century of research, aspirin/SA’s mechanism(s) of action is still only partially understood. Here we report the results of a genome-wide, high-throughput screen to identify potential SA-binding proteins (SABPs) in human HEK293 cells. Following photo-affinity crosslinking to 4-azidoSA and immuno-selection with an anti-SA antibody, approximately 2,000 proteins were identified. Among these, 95 were enriched more than 10-fold. Pathway enrichment analysis with these 95 candidate SABPs (cSABPs) revealed possible involvement of SA in multiple biological pathways, including (i) glycolysis, (ii) cytoskeletal assembly and/or signaling, and (iii) NF-κB-mediated immune signaling. The two most enriched cSABPs, which corresponded to the glycolytic enzymes alpha-enolase (ENO1) and pyruvate kinase isozyme M2 (PKM2), were assessed for their ability to bind SA and SA’s more potent derivative amorfrutin B1 (amoB1). SA and amoB1 bound recombinant ENO1 and PKM2 at low millimolar and micromolar concentrations, respectively, and inhibited their enzymatic activities in vitro. Consistent with these results, low millimolar concentrations of SA suppressed glycolytic activity in HEK293 cells. To provide insights into how SA might affect various human diseases, a cSABP-human disorder/disease network map was also generated.

【 授权许可】

CC BY