HIPK2 phosphorylates HDAC3 for NF-κB acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis

This is the authors' abstract. We don't add key points for this paper.

Significance Multiple human diseases including cancer and sepsis are closely related to uncontrolled inflammation. However, there is not much success for clinical therapy to date by targeting specific inflammatory cytokines. Since NF-κB–mediated transactivation in the nucleus is pivotal downstream of various stimuli to induce inflammation, searching the nuclear-localized targets specifically regulating NF-κB activation will provide important therapeutic application. This study has found that HIPK2 restrains NF-κB activation through phosphorylating HDAC3 at serine 374 to inactive HDAC3 deacetylase activity, thus reducing the p65 deacetylation and suppressing inflammation. Our findings reveal a function of the HIPK2-HDAC3-p65 module in macrophages to restrain excessive inflammation, which may represent a therapeutic mechanism for inflammation-related diseases.