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

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 S...

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Published in分子细胞生物学报：英文版 Vol. 9; no. 2; pp. 144 - 153
Main Author Tingting Yu Yong Zuo Rong Cai Xian Huang Shuai Wu Chenxi Zhang Y. Eugene Chin Dongdong Li Zhenning Zhang Nansong Xia Qi Wang Hao Shen Xuebiao Yao Zhong-Yin Zhang Song Xue Lei Shen Jinke Cheng
Format Journal Article
LanguageEnglish
Published 2017
Subjects
IFN-γ
IFNγ
STAT3
反馈回路
巨噬细胞
细胞内信号转导
细胞活化
蛋白酪氨酸磷酸酶
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Summary: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 （PTPIB）, in IFN-y 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 macro- phages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listerio rnonocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in rnacrophage polarization.
Bibliography:IFN-γ, macrophage, SENP1, SUMOylation
31-2002/Q
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 （PTPIB）, in IFN-y 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 macro- phages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listerio rnonocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in rnacrophage polarization.
ISSN:1674-2788
1759-4685