Browsing by Author "Zhang, Zhenning"

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    SENP1 regulates IFN-γ−STAT1 signaling through STAT3−SOCS3 negative feedback loop
    (Oxford, 2017-04) Yu, Tingting; Zuo, Yong; Cai, Rong; Huang, Xian; Wu, Shuai; Zhang, Chenxi; Chin, Y. Eugene; Li, Dongdong; Zhang, Zhenning; Xia, Nansong; Wang, Qi; Shen, Hao; Yao, Xuebiao; Zhang, Zhong-Yin; Xue, Song; Shen, Lei; Cheng, Jinke; Biochemistry and Molecular Biology, School of Medicine
    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.