SENP1 regulates IFN-γ−STAT1 signaling through STAT3−SOCS3 negative feedback loop. (26th October 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of molecular cell biology. Volume 9:Number 2(2017:Apr.)
• Page Start: 144
• Page End: 153
• Publication Date: 2016-10-26
• Subjects: IFN-γ -- macrophage -- SENP1 -- SUMOylation; Molecular biology -- Periodicals; 571.605
• DOI: 10.1093/jmcb/mjw042
• Languages: English
• ISSNs: 1674-2788

Abstract

Abstract: 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.