| 1 | The deubiquitinase OTUD1 inhibits colonic inflammation by suppressing RIPK1-mediated NF-κB signaling显示文摘The E3 ubiquitin ligase(E3)-mediated ubiquitination and deubiquitinase(DUB)-mediated deubiquitination processes are closely associated with the occurrence and development of colonic inflammation.Ovarian tumor deubiquitinase 1(OTUD1)is involved in immunoregulatory functions linked to infectious diseases.However,the effect of OTUD1 on intestinal immune responses during colonic inflammatory disorders such as inflammatory bowel disease(IBD)remains unclear.Here,we show that loss of OTUD1 in mice contributes to the pathogenesis of dextran sulfate sodium(DSS)-induced colitis via excessive release of proinflammatory cytokines.In addition,bone marrow transplantation experiments revealed that OTUD1 in hematopoietic cells plays a dominant role in protection against colitis.Mechanistically,OTUD1 physically interacts with receptor-interacting serine/threonine-protein kinase 1(RIPK1)and selectively cleaves K63-linked polyubiquitin chains from RIPK1 to inhibit the recruitment of NF-κB essential modulator(NEMO).Moreover,the expression of OTUD1 in mucosa samples from ulcerative colitis(UC)patients was lower than that in mucosa samples from healthy controls.Furthermore,we demonstrate that the UC-associated OTUD1 G430V mutation abolishes the ability of OTUD1 to inhibit RIPK1-mediated NF-κB activation and intestinal inflammation.Taken together,our study unveils a previously unexplored role of OTUD1 in moderating intestinal inflammation by inhibiting RIPK1-mediated NF-κB activation,suggesting that the OTUD1-RIPK1 axis could be a potential target for the treatment of IBD. | Bo Wu Lihua Qiang Yong Zhang Yesheng Fu Mengyuan Zhao Zehui Lei Zhe Lu Yan-Ge Wei Hongmiao Dai Yingwei Ge Mingqiu Liu Xuemei Zhou Zhiqiang Peng Hongchang Li Chun-Ping Cui Jing Wang Hui Zheng Cui Hua Liu Lingqiang Zhang | 2022 | Cellular & Molecular Immunology2022，19，2： | 3 |
| 4 | IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation显示文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy. | WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI ZHAO | 2024 | Oncology Research2024，32，4： | 0 |
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