SENP1 regulates IFN-γ-STAT1 signaling through STAT3-SOCS3 negative feedback loop

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2017,（2）
• 页码范围: 144-153
• 页数: 10页
• 语种: 英文
• DOI: 10.1093/jmcb/mjw042

摘要

Interferon-γ (IFN-γ) triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling.Suppressor of cytokine signaling 1 (SOCS1) and protein tyrosine phosphatases can negatively modulate IFN-γ signaling.Here,we identify a novel negative feedback loop mediated by STAT3-SOCS3,which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B (PTP1B),in IFN-γ signaling.SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation.PTP1B in SENP1-deficient macrophages is highly SUMOylated,which reduces PTP1B-induced de-phosphorylation of STAT3.Activated STAT3 then suppresses STAT1 activation via SOCS3 induction in SENP1-deficient macrophages.Accordingly,SENP1-deficient macrophages show reduced ability to resist Listeria monocytogenes infection.These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in macrophage polarization.