Abstract
Inhibitors of checkpoint kinase 1 (CHK1), a central component of DNA damage and cell cycle checkpoint response, represent a promising new cancer therapy, but the global cellular functions they regulate through phosphorylation are poorly understood. To elucidate the CHK1-regulated phosphorylation network, we performed a global quantitative phosphoproteomics analysis, which revealed 142 phosphosites whose phosphorylation levels were significantly different following treatment with the CHK1 inhibitor SCH 900776. Bioinformatics analysis identified phosphoproteins that function in ATR-CHK1 signaling, DNA replication, and DNA repair. Furthermore, IRF3 phosphorylation at S173 and S175 was significantly reduced following treatment with SCH 900776. Our findings indicate that the CHK1-dependent regulation of IRF3 phosphorylation at S173 and S175 may play a role in the induction of innate immune response after replication stress or DNA damage, which suggests a potential function of CHK1 in the innate immune response. Data are available via ProteomeXchange with identifier PXD015125.
Original language | English (US) |
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Pages (from-to) | 2264-2277 |
Number of pages | 14 |
Journal | Journal of Proteome Research |
Volume | 19 |
Issue number | 6 |
DOIs | |
State | Published - Jun 5 2020 |
Keywords
- CHK1
- CHK1 kinase inhibitor
- IRF3
- Phosphoproteomics
- innate immunity
ASJC Scopus subject areas
- Biochemistry
- General Chemistry