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. Data are available
via ProteomeXchange with identifier PXD015125.