| First Author | Yu T | Year | 2017 |
| Journal | J Mol Cell Biol | Volume | 9 |
| Issue | 2 | Pages | 144-153 |
| PubMed ID | 27702761 | Mgi Jnum | J:330454 |
| Mgi Id | MGI:6882923 | Doi | 10.1093/jmcb/mjw042 |
| Citation | Yu T, et al. (2017) SENP1 regulates IFN-gamma-STAT1 signaling through STAT3-SOCS3 negative feedback loop. J Mol Cell Biol 9(2):144-153 |
| abstractText | Interferon-gamma (IFN-gamma) 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-gamma 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-gamma signaling. SENP1-deficient macrophages show defects in IFN-gamma 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. |
