10 results on '"Tong, Wu"'
Search Results
2. 2AB protein of Senecavirus A antagonizes selective autophagy and type I interferon production by degrading LC3 and MARCHF8
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Sun, Dage, primary, Kong, Ning, additional, Dong, Sujie, additional, Chen, Xiaoyong, additional, Qin, Wenzhen, additional, Wang, Hua, additional, Jiao, Yajuan, additional, Zhai, Huanjie, additional, Li, Liwei, additional, Gao, Fei, additional, Yu, Lingxue, additional, Zheng, Hao, additional, Tong, Wu, additional, Yu, Hai, additional, Zhang, Wen, additional, Tong, Guangzhi, additional, and Shan, Tongling, additional
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- 2021
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3. 2AB protein of Senecavirus A antagonizes selective autophagy and type I interferon production by degrading LC3 and MARCHF8.
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Sun, Dage, Kong, Ning, Dong, Sujie, Chen, Xiaoyong, Qin, Wenzhen, Wang, Hua, Jiao, Yajuan, Zhai, Huanjie, Li, Liwei, Gao, Fei, Yu, Lingxue, Zheng, Hao, Tong, Wu, Yu, Hai, Zhang, Wen, Tong, Guangzhi, and Shan, Tongling
- Subjects
AUTOPHAGY ,TUBULINS ,SMALL interfering RNA ,VIRAL nonstructural proteins ,TYPE I interferons ,TISSUE culture - Abstract
Senecavirus A (SVA), an important emerging porcine virus, has outbreaks in different regions and countries each year, becoming a virus with global prevalence. SVA infection has been reported to induce macroautophagy/autophagy; however, the molecular mechanisms of autophagy induction and the effect of SVA on autophagy remain unknown. This study showed that SVA infection induced the autophagy process in the early stage of SVA infection, and the rapamycin-induced autophagy inhibited SVA replication by degrading virus 3 C protein. To counteract this, SVA utilized 2AB protein inhibiting the autophagy process from promoting viral replication in the late stage of SVA infection. Further study showed that SVA 2AB protein interacted with MARCHF8/MARCH8 and LC3 to degrade the latter and inhibit the autophagy process. In addition, we found that MARCHF8 was a positive regulator of type I IFN (IFN-I) signaling. During the autophagy process, the SVA 2AB protein targeted MARCHF8 and MAVS forming a large complex for degradation to deactivate IFN-I signaling. Together, our study reveals the molecular mechanisms of selective autophagy in the host against viruses and reveals potential viral strategies to evade the autophagic process and IFN-I signaling for successful pathogenesis. Abbreviations: Baf A
1 : bafilomycin A1 ; Co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4′,6-diamidino-2-phenylindole; hpi: hours post-infection; IFN: interferon; ISG: IFN-stimulated gene; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF8/MARCH8: membrane associated ring-CH-type finger 8; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; Rapa: rapamycin; RT: room temperature; siRNA: small interfering RNA; SVA: Senecavirus A; TCID50 : 50% tissue culture infectious doses. [ABSTRACT FROM AUTHOR]- Published
- 2022
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4. BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy
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Kong, Ning, primary, Shan, Tongling, additional, Wang, Hua, additional, Jiao, Yajuan, additional, Zuo, Yewen, additional, Li, Liwei, additional, Tong, Wu, additional, Yu, Lingxue, additional, Jiang, Yifeng, additional, Zhou, Yanjun, additional, Li, Guoxin, additional, Gao, Fei, additional, Yu, Hai, additional, Zheng, Hao, additional, and Tong, Guangzhi, additional
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- 2019
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5. BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy.
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Kong, Ning, Shan, Tongling, Wang, Hua, Jiao, Yajuan, Zuo, Yewen, Li, Liwei, Tong, Wu, Yu, Lingxue, Jiang, Yifeng, Zhou, Yanjun, Li, Guoxin, Gao, Fei, Yu, Hai, Zheng, Hao, and Tong, Guangzhi
- Subjects
PORCINE epidemic diarrhea virus ,VIRAL replication ,NUCLEOCAPSIDS ,AUTOPHAGY ,IMMUNE response ,ANTIVIRAL agents - Abstract
Interferon-induced BST2 (bone marrow stromal cell antigen 2) inhibits viral replication by tethering enveloped virions to the cell surface to restrict viral release and by inducing the NFKB-dependent antiviral immune response. However, the mechanism by which BST2 uses the selective autophagy pathway to inhibit viral replication is poorly understood. In this study, we showed that BST2 expression was significantly increased during porcine epidemic diarrhea virus (PEDV) infection of Vero cells by IRF1 targeting its promoter. We also showed that BST2 suppressed PEDV replication by binding and degrading the PEDV-encoded nucleocapsid (N) protein. The downregulation of N protein was blocked by macroautophagy/autophagy inhibitors but not a proteasome inhibitor, implying that the N protein was degraded via the selective autophagy pathway. Both the BST2 and N protein interacted with the E3 ubiquitin ligase MARCHF8/MARCH8 and the cargo receptor CALCOCO2/NDP52, and the ubiquitination of N protein was necessary for the degradation of N mediated by the BST2-MARCHF8 axis. The knockdown of MARCHF8 or ATG5 with small interfering RNAs blocked the selective autophagy pathway, rescued the protein abundance of PEDV N in 293T cells, and prevented the inhibition of PEDV replication by BST2 in Vero cells. Together, our data demonstrate the novel mechanism of BST2-mediated virus restriction, in which BST2 recruits MARCHF8 to catalyze the ubiquitination of the PEDV N protein. The ubiquitinated N protein is then recognized by CALCOCO2/NDP52, which delivers it to autolysosome for degradation through the selective autophagy pathway. Abbreviations: 3MA: 3-methyladenine; ATG: autophagy-related; Baf A1: bafilomycin A
1 ; BST2: bone marrow stromal cell antigen 2; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CC: coiled-coil; ChIP: chromatin immunoprecipitation; Co-IP: co-immunoprecipitation; CQ: chloroquine; CT: cytoplasmic tail; DAPI: 4′,6-diamidino-2-phenylindole; GPI: glycosyl-phosphatidylinositol; hpi: hours post infection; IRF1: interferon regulatory factor 1; ISG: IFN-stimulated gene; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF8/MARCH8: membrane-associated ring-CH-type finger 8; MOI: multiplicity of infection; N protein: nucleocapsid protein; PED: porcine epidemic diarrhea; PEDV: porcine epidemic diarrhea virus; RT: room temperature; siRNA: small interfering RNA; STAT: signal transducer and activator of transcription; TCID50 : 50% tissue culture infectious doses; TM: transmembrane. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Impaired autophagy due to constitutive mTOR activation sensitizes TSC2-null cells to cell death under stress
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Han-Ming Shen, Shukie Ng, You-Tong Wu, Bo Chen, and Jing Zhou
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congenital, hereditary, and neonatal diseases and abnormalities ,Programmed cell death ,Time Factors ,Cell Survival ,mTORC1 ,Biology ,Mechanistic Target of Rapamycin Complex 1 ,Autophagy-Related Protein 7 ,Cell Line ,Mice ,Null cell ,Autophagy ,Animals ,Transgenes ,RNA, Small Interfering ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cell Death ,TOR Serine-Threonine Kinases ,Proteins ,Chloroquine ,Cell Biology ,Fibroblasts ,nervous system diseases ,Cell biology ,Cell culture ,Apoptosis ,Multiprotein Complexes ,Cancer research ,Microtubule-Associated Proteins ,Signal Transduction - Abstract
It has been well documented that cells deficient in either TSC1 or TSC2 are highly sensitive to various cell death stimuli. In this study, we utilized the TSC2 (-/-) mouse embryonic fibroblasts (MEFs) to study the involvement of autophagy in the enhanced susceptibility of TSC2-null cells to cell death. We first confirmed that both TSC1-null and TSC2-null MEFs are more sensitive to apoptosis in response to amino acid starvation (EBSS) and hypoxia. Second, we found that both the basal and inducible autophagy in TSC2 (-/-) MEFs is impaired, mainly due to constitutive activation of mTORC1. Third, suppression of autophagy by chloroquine and Atg7 knockdown sensitizes TSC2 (+/+) cells, but not TSC2 (-/-) cells, to EBSS-induced cell death. Conversely, the inhibition of mTORC1 by raptor knockdown and rapamycin activates autophagy and subsequently rescues TSC2 (-/-) cells. Finally, in starved cells, nutrient supplementations (insulin-like growth factor-1 (IGF-1) and leucine) enhanced cell death in TSC2 (-/-) cells, but reduced cell death in TSC2 (+/+) cells. Taken together, these data indicate that constitutive activation of mTORC1 in TSC2 (-/-) cells leads to suppression of autophagy and enhanced susceptibility to stress-mediated cell death. Our findings thus provide new insights into the complex relationships among mTOR, autophagy and cell death, and support the possible autophagy-targeted intervention strategies for the treatment of TSC-related pathologies.
- Published
- 2011
7. Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy
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Hui-Ling Tan, Qing Huang, Choon Nam Ong, You-Tong Wu, and Han-Ming Shen
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Programmed cell death ,Necrosis ,medicine.medical_treatment ,Biology ,Models, Biological ,chemistry.chemical_compound ,Mice ,Phosphatidylinositol 3-Kinases ,medicine ,Autophagy ,Animals ,Insulin ,LY294002 ,Insulin-Like Growth Factor I ,Molecular Biology ,Protein kinase B ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Phosphoinositide-3 Kinase Inhibitors ,Epidermal Growth Factor ,TOR Serine-Threonine Kinases ,Cell Biology ,Cell biology ,Enzyme Activation ,chemistry ,Cytoprotection ,Gene Knockdown Techniques ,medicine.symptom ,Signal transduction ,Protein Kinases ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Our previous work has shown that autophagy plays a pro-survival function in two necrotic cell death models: zVAD-treated L929 cells as well as H(2)O(2)-treated Bax(-/-)Bak(-/-) mouse embryonic fibroblasts (DKO MEF). This study aims to further explore the regulatory role of autophagy in necrosis by examining the functional role of the phosphoinositide-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway. Our initial intriguing finding was that insulin is able to promote necrotic cell death induced by zVAD and MNNG in L929 cells or by H(2)O(2) in DKO MEF cells cultured in full-growth medium. The pro-necrosis function of insulin was further supported by the observations that insulin is capable of abolishing the protective effect of starvation on necrotic cell death induced by zVAD in L929 cells. Next, we demonstrated that insulin acts on the PI3K-Akt-mTOR pathway to promote necrosis as the suppression of the above pathway by either chemical inhibitors (LY294002 and rapamycin) or mTOR knockdown is able to mitigate the pro-death function of insulin. Finally, we provided evidence that the pro-death function of insulin is dependent on its inhibitory effect on autophagy, which serves as an important pro-survival function in necrosis. Taken together, here we provide compelling evidence to show that activation of the PI3K-Akt-mTOR signaling pathway can promote necrotic cell death via suppression of autophagy, at least in the necrosis models defined in our study in which autophagy serves as a pro-survival function. Data from this study not only further underscore the pro-survival function of autophagy in necrotic cell death, but also provide a novel insight into the intricate connections linking the PI3K-Akt-mTOR signaling pathway with cell death via modulation of autophagy.
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- 2009
8. Autophagy plays a protective role during zVAD-induced necrotic cell death
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Hui-Ling Tan, Zheng-gang Liu, You-Tong Wu, Wei-Yi Ong, You-Sun Kim, Ning Pan, Qing Huang, Han-Ming Shen, and Choon Nam Ong
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Programmed cell death ,Necrosis ,Autophagosome maturation ,ATG5 ,Biology ,Cysteine Proteinase Inhibitors ,Autophagy-Related Protein 7 ,Amino Acid Chloromethyl Ketones ,Autophagy-Related Protein 5 ,Cell Line ,Mice ,Phagosomes ,medicine ,Autophagy ,Animals ,Humans ,Molecular Biology ,Sirolimus ,U937 cell ,Proteins ,Chloroquine ,Cell Biology ,Fibroblasts ,Caspase Inhibitors ,Cathepsins ,Cell biology ,Cell culture ,Gene Targeting ,Beclin-1 ,medicine.symptom ,Apoptosis Regulatory Proteins ,Lysosomes ,Microtubule-Associated Proteins ,Biomarkers - Abstract
The aim of this study is to examine the role of autophagy in cell death by using a well-established system in which zVAD, a pan-caspase inhibitor, induces necrotic cell death in L929 murine fibrosarcoma cells. First, we observed the presence of autophagic hallmarks, including an increased number of autophagosomes and the accumulation of LC3-II in zVAD-treated L929 cells. Since the presence of such autophagic hallmarks could be the result of either increased flux of autophagy or blockage of autophagosome maturation (lysosomal fusion and degradation), we next tested the effect of rapamycin, a specific inhibitor for mTOR, and chloroquine, a lysosomal enzyme inhibitor, on zVAD-induced cell death. To our surprise, rapamycin, known to be an autophagy inducer, blocked zVAD-induced cell death, whereas chloroquine greatly sensitized zVAD-induced cell death in L929 cells. Moreover, similar results with rapamycin and chloroquine were also observed in U937 cells when challenged with zVAD. Consistently, induction of autophagy by serum starvation offered significant protection against zVAD-induced cell death, whereas knockdown of Atg5, Atg7 or Beclin 1 markedly sensitized zVAD-induced cell death in L929 cells. More importantly, Atg genes knockdown completely abolished the protective effect of serum starvation on zVAD-induced cell death. Finally, we demonstrated that zVAD was able to inhibit lysosomal enzyme cathepsin B activity, and subsequently blocked autophagosome maturation. Taken together, in contrast to the previous conception that zVAD induces autophagic cell death, here we provide compelling evidence suggesting that autophagy serves as a cell survival mechanism and suppression of autophagy via inhibition of lysosomal function contributes to zVAD-induced necrotic cell death.
- Published
- 2008
9. Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53.
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Kaipeng Jing, Kyoung-Sub Song, Soyeon Shin, Nayeong Kim, Soyeon Jeong, Hye-Rim Oh, Ji-hoon Park, Kang-Sik Seo, Jun-Young Heo, Jeongsu Han, Jong-Il Park, Chang Han, Tong Wu, Gi-Ryang Kweon, Seung-Kiel Park, Wan-hee Yoon, Byung-Doo Hwang, and Kyu Lim
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- 2011
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10. Impaired autophagy due to constitutive mTOR activation sensitizes TSC2-null cells to cell death under stress.
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Shukie Ng, You-Tong Wu, Bo Chen, Jing Zhou, and Han-Ming Shen
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- 2011
- Full Text
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