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

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

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)144-153
Number of pages10
JournalJournal of Molecular Cell Biology
Volume9
Issue number2
DOIs
StatePublished - 2017

Keywords

  • IFN-γ
  • Macrophage
  • SENP1
  • SUMOylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Yu, T., Zuo, Y., Cai, R., Huang, X., Wu, S., Zhang, C., Chin, Y. E., Li, D., Zhang, Z., Xia, N., Wang, Q., Shen, H., Yao, X., Zhang, Z. Y., Xue, S., Shen, L., & Cheng, J. (2017). SENP1 regulates IFN-γ-STAT1 signaling through STAT3-SOCS3 negative feedback loop. Journal of Molecular Cell Biology, 9(2), 144-153. https://doi.org/10.1093/jmcb/mjw042