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Correlation between TGF ‐β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain‐like protease
Author(s) -
Li ShihWen,
Yang TsueyChing,
Wan Lei,
Lin YingJu,
Tsai FuuJen,
Lai ChienChen,
Lin ChengWen
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201200225
Subject(s) - microbiology and biotechnology , biology , proteasome , downregulation and upregulation , vimentin , deubiquitinating enzyme , signal transduction , ubiquitin , chemistry , biochemistry , immunology , gene , immunohistochemistry
Severe acute respiratory syndrome ( SARS ) coronavirus ( SARS ‐ C o V ) papain‐like protease ( PL pro), a deubiquitinating enzyme, demonstrates inactivation of interferon ( IFN ) regulatory factor 3 and NF ‐κ B , reduction of IFN induction, and suppression of type I IFN signaling pathway. This study investigates cytokine expression and proteomic change induced by SARS ‐ C o V PL pro in human promonocyte cells. PLpro significantly increased TGF ‐β1 m RNA expression (greater than fourfold) and protein production (greater than threefold). Proteomic analysis, W estern blot, and quantitative real‐time PCR assays indicated PL pro upregulating TGF ‐β1‐associated genes: HSP 27, protein disulfide isomerase A 3 precursor, glial fibrillary acidic protein, vimentin, retinal dehydrogenase 2, and glutathione transferase omega‐1. PLpro‐activated ubiquitin proteasome pathway via upregulation of ubiquitin‐conjugating enzyme E 2–25k and proteasome subunit alpha type 5. Proteasome inhibitor MG ‐132 significantly reduced expression of TGF ‐β1 and vimentin. PL pro upregulated HSP 27, linking with activation of p38 MAPK and ERK 1/2 signaling. Treatment with SB 203580 and U 0126 reduced PL pro‐induced expression of TGF ‐β1, vimentin, and type I collagen. Results point to SARS ‐ C o V PL pro triggering TGF ‐β1 production via ubiquitin proteasome, p38 MAPK , and ERK 1/2‐mediated signaling.