| Literature DB >> 27702761 |
Tingting Yu1,2,3, Yong Zuo1,2, Rong Cai1,2, Xian Huang1,2, Shuai Wu4, Chenxi Zhang5, Y Eugene Chin5, Dongdong Li1, Zhenning Zhang1, Nansong Xia1, Qi Wang1, Hao Shen6, Xuebiao Yao7, Zhong-Yin Zhang8, Song Xue9, Lei Shen1,4, Jinke Cheng1,2,3.
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.Entities:
Keywords: IFN-γ; SENP1; SUMOylation; macrophage
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Year: 2017 PMID： 27702761 PMCID： PMC7104919 DOI： 10.1093/jmcb/mjw042
Source DB: PubMed Journal: J Mol Cell Biol ISSN： 1759-4685 Impact factor: 6.216