Proteome, Lysine Acetylome, and Succinylome Identify Posttranslational Modification of STAT1 as a Novel Drug Target in Silicosis.
Mol Cell Proteomics
; 23(6): 100770, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38641226
ABSTRACT
Inhalation of crystalline silica dust induces incurable lung damage, silicosis, and pulmonary fibrosis. However, the mechanisms of the lung injury remain poorly understood, with limited therapeutic options aside from lung transplantation. Posttranslational modifications can regulate the function of proteins and play an important role in studying disease mechanisms. To investigate changes in posttranslational modifications of proteins in silicosis, combined quantitative proteome, acetylome, and succinylome analyses were performed with lung tissues from silica-injured and healthy mice using liquid chromatography-mass spectrometry. Combined analysis was applied to the three omics datasets to construct a protein landscape. The acetylation and succinylation of the key transcription factor STAT1 were found to play important roles in the silica-induced pathophysiological changes. Modulating the acetylation level of STAT1 with geranylgeranylacetone effectively inhibited the progression of silicosis. This report revealed a comprehensive landscape of posttranslational modifications in silica-injured mouse and presented a novel therapeutic strategy targeting the posttranslational level for silica-induced lung diseases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Silicosis
/
Protein Processing, Post-Translational
/
Proteome
/
STAT1 Transcription Factor
/
Lysine
Limits:
Animals
Language:
En
Journal:
Mol Cell Proteomics
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2024
Document type:
Article
Affiliation country:
China