Phospho-proteomic Analyses Provide Insight into Underlying Molecular Mechanisms of NETosis

ABSTRACT: NETosis, a novel cell death leads to neutrophil extracellular trap (NET) formation, is involved in both infectious and noninfectious disease. However, mechanisms underlying NETosis remain unclear. To explore the underlying molecular mechanisms and common factors associated with both NOX-dependent and NOX-independent NETosis, we conducted global proteomics and phospho-proteomics analyses of phorbol 12-myristate 13-acetate (PMA)-, ionomycin-, and monosodium urate (MSU) - induced early stage NETosis. Global proteomic analyses identified 64, 97, and 141 proteins differentially regulated in the PMA, ionomycin, and MSU comparisons with the control, respectively. Next, phospho-proteomic analyses identified: 931, 565 and 201 phosphorylation sites differentially regulated in the PMA, ionomycin, and MSU comparisons with the control, respectively. Furthermore, overlap analysis of the three comparisons identified 9 proteins and 49 phosphorylation sites derived from 41 phosphoproteins. Among the 41 differentially regulated phosphoproteins, 23 were associated with the nucleus, 5 with chromatin binding and 13 with poly(A) RNA binding according to GO annotation. Of which, DEK, Methyl-CpG-binding protein 2 (MECP2) and structure-specific recognition protein 1 (SSRP1) involved in both chromatin and poly(A) RNA binding. In conclusion, our study provides insight into molecular mechanisms of NETosis and this dataset will be benefit for further elucidation.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jinjun Chen  

PROVIDER: PXD014418 | iProX | Thu Jun 27 00:00:00 BST 2019

REPOSITORIES: iProX