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Phosphoproteomics Analysis Reveals a Potential Role of CHK1 in Regulation of Innate Immunity through IRF3

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.

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Cat.No. Product Name Information Publications Customer Product Validation
S2735 MK-8776 (SCH 900776) MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2. (46) (6)

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