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Shao-Cong Sun

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https://www.readbyqxmd.com/read/30054854/deubiquitinases-as-pivotal-regulators-of-t-cell-functions
#1
REVIEW
Xiao-Dong Yang, Shao-Cong Sun
T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in Tcell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs)...
July 27, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/30054192/7%C3%AE-methyl-substituent-is-a-structural-locus-associated-with-activity-cliff-for-nepenthone-analogues
#2
Hui-Jiao Sun, Yu-Hua Wang, Cong-Min Yuan, Ling-Hui Kong, Xue-Jun Xu, Yu-Jun Wang, Hai-Hao Wu, Cheng Lin, Yuan-Yuan Qian, Huo-Ming Huang, Li Xiao, Xiao Liu, Qian He, Sheng-Yang Fang, Deng-Qi Xue, Xi-Cheng Yang, Hao Chen, Yi-Lin Zheng, Lan Zheng, Lin-Qian Yu, Qiong Xie, Wei Fu, Wei Li, Jing-Gen Liu, Zhui-Bai Qiu, Li-Ming Shao
With the purpose of identifying novel selective κ opioid receptor (KOR) antagonists as potential antidepressants from nepenthone analogues, starting from N-nor-N-cyclopropylmethyl-nepenthone (SLL-020ACP), a highly selective and potent KOR agonist, a series of 7β-methyl-nepenthone analogues was conceived, synthesized and assayed on opioid receptors based on the concept of hybridization. According to the pharmacological results, the functional reversal observed in orvinol analogues by introduction of 7β-methyl substituent could not be reproduced in nepenthone analogues...
July 24, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/30022064/tbk-binding-protein-1-regulates-il-15-induced-autophagy-and-nkt-cell-survival
#3
Lele Zhu, Xiaoping Xie, Lingyun Zhang, Hui Wang, Zuliang Jie, Xiaofei Zhou, Jianhong Shi, Shuli Zhao, Boxiang Zhang, Xuhong Cheng, Shao-Cong Sun
The cytokine IL-15 mediates development and survival of immune cells, including natural killer T (NKT) cells, but the underlying mechanism of IL-15 function is incompletely understood. Here we show that IL-15 induces autophagy in NKT cells with a mechanism that involves a crucial signaling component, TBK-binding protein 1 (Tbkbp1). Tbkbp1 facilitates activation of the autophagy-initiating kinase Ulk1 through antagonizing the inhibitory action of mTORC1. This antagonization involves the recruitment of an mTORC1-opposing phosphatase to Ulk1...
July 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789521/triad3a-induces-the-degradation-of-early-necrosome-to-limit-ripk1-dependent-cytokine-production-and-necroptosis
#4
Norah A Alturki, Scott McComb, Ardeshir Ariana, Dikchha Rijal, Robert G Korneluk, Shao-Cong Sun, Emad Alnemri, Subash Sad
Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29726618/metformin-s-antitumour-and-anti-angiogenic-activities-are-mediated-by-skewing-macrophage-polarization
#5
Ji-Chang Wang, Xin Sun, Qiang Ma, Gui-Feng Fu, Long-Long Cong, Hong Zhang, De-Fu Fan, Jun Feng, Shao-Ying Lu, Jian-Lin Liu, Guang-Yue Li, Pei-Jun Liu
Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells...
May 4, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29669287/zranb1-is-an-ezh2-deubiquitinase-and-a-potential-therapeutic-target-in-breast-cancer
#6
Peijing Zhang, Zhenna Xiao, Shouyu Wang, Mutian Zhang, Yongkun Wei, Qinglei Hang, Jongchan Kim, Fan Yao, Cristian Rodriguez-Aguayo, Baochau N Ton, Minjung Lee, Yumeng Wang, Zhicheng Zhou, Liyong Zeng, Xiaoyu Hu, Sarah E Lawhon, Ashley N Siverly, Xiaohua Su, Jia Li, Xiaoping Xie, Xuhong Cheng, Liang-Chiu Liu, Hui-Wen Chang, Shu-Fen Chiang, Gabriel Lopez-Berestein, Anil K Sood, Junjie Chen, M James You, Shao-Cong Sun, Han Liang, Yun Huang, Xianbin Yang, Deqiang Sun, Yutong Sun, Mien-Chie Hung, Li Ma
Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669285/kap1-regulates-regulatory-t-cell-function-and-proliferation-in-both-foxp3-dependent-and-independent-manners
#7
Shigeru Tanaka, Christian Pfleger, Jen-Feng Lai, Florence Roan, Shao-Cong Sun, Steven F Ziegler
Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29651155/epigenetic-activation-during-t-helper-17-cell-differentiation-is-mediated-by-tripartite-motif-containing-28
#8
Yu Jiang, Ying Liu, Huiping Lu, Shao-Cong Sun, Wei Jin, Xiaohu Wang, Chen Dong
Epigenetic regulation is important for T-cell fate decision. Although STAT3 is known to initiate Th17 differentiation program, the downstream mechanism is unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in Th17 cells is required for Th17-mediated cytokine production and experimental autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound regions overlap with almost all Th17-specific super-enhancers (SE), and that those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of RORγt...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29618817/fatal-swine-acute-diarrhoea-syndrome-caused-by-an-hku2-related-coronavirus-of-bat-origin
#9
Peng Zhou, Hang Fan, Tian Lan, Xing-Lou Yang, Wei-Feng Shi, Wei Zhang, Yan Zhu, Ya-Wei Zhang, Qing-Mei Xie, Shailendra Mani, Xiao-Shuang Zheng, Bei Li, Jin-Man Li, Hua Guo, Guang-Qian Pei, Xiao-Ping An, Jun-Wei Chen, Ling Zhou, Kai-Jie Mai, Zi-Xian Wu, Di Li, Danielle E Anderson, Li-Biao Zhang, Shi-Yue Li, Zhi-Qiang Mi, Tong-Tong He, Feng Cong, Peng-Ju Guo, Ren Huang, Yun Luo, Xiang-Ling Liu, Jing Chen, Yong Huang, Qiang Sun, Xiang-Li-Lan Zhang, Yuan-Yuan Wang, Shao-Zhen Xing, Yan-Shan Chen, Yuan Sun, Juan Li, Peter Daszak, Lin-Fa Wang, Zheng-Li Shi, Yi-Gang Tong, Jing-Yun Ma
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms...
April 2018: Nature
https://www.readbyqxmd.com/read/29604293/immune-cell-production-of-interleukin-17-induces-stem-cell-features-of-pancreatic-intraepithelial-neoplasia-cells
#10
Yu Zhang, Michelle Zoltan, Erick Riquelme, Hanwen Xu, Ismet Sahin, Susana Castro-Pando, Maria Fernanda Montiel, Kyle Chang, Zhengyu Jiang, Jianhua Ling, Sonal Gupta, William Horne, Melissa Pruski, Huamin Wang, Shao-Cong Sun, Guillermina Lozano, Paul Chiao, Anirban Maitra, Steven D Leach, Jay K Kolls, Eduardo Vilar, Timothy C Wang, Jennifer M Bailey, Florencia McAllister
BACKGROUND & AIMS: Little is known about how the immune system affects stem cell features of pancreatic cancer cells. Immune cells that produce interleukin 17A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to pancreatic interepithelial neoplasia (PanIN) initiation and progression. We investigated the effects that IL17A signaling exerts on pancreatic cancer progenitor cells and the clinical relevance of this phenomena. METHODS: We performed studies with Mist1Cre;LSLKras;Rosa26mTmG (KCiMist ;G) and Kras(G12D);Trp53(R172H);Pdx1-Cre (KPC) mice (which upon tamoxifen induction spontaneously develop PanINs) and control littermates...
July 2018: Gastroenterology
https://www.readbyqxmd.com/read/29555915/peli1-negatively-regulates-noncanonical-nf-%C3%AE%C2%BAb-signaling-to-restrain-systemic-lupus-erythematosus
#11
Junli Liu, Xinfang Huang, Shumeng Hao, Yan Wang, Manman Liu, Jing Xu, Xingli Zhang, Tao Yu, Shucheng Gan, Dongfang Dai, Xuan Luo, Qingyan Lu, Chaoming Mao, Yanyun Zhang, Nan Shen, Bin Li, Mingzhu Huang, Xiaodong Zhu, Jin Jin, Xuhong Cheng, Shao-Cong Sun, Yichuan Xiao
Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling...
March 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29532562/activation-of-ampk-by-simvastatin-inhibited-breast-tumor-angiogenesis-via-impeding-hif-1%C3%AE-induced-pro-angiogenic-factor
#12
Ji-Chang Wang, Xiong-Xiong Li, Xin Sun, Guang-Yue Li, Jing-Lan Sun, Yuan-Peng Ye, Long-Long Cong, Wei-Ming Li, Shao-Ying Lu, Jun Feng, Pei-Jun Liu
Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell-conditioned medium-induced angiogenic promotion in vitro, and resulted in dose-dependent anti-angiogenesis in vivo...
May 2018: Cancer Science
https://www.readbyqxmd.com/read/29523541/peli1-modulates-the-subcellular-localization-and-activity-of-mdmx
#13
Dawei Li, Omid Tavana, Shao-Cong Sun, Wei Gu
Mdm2 and Mdmx, both major repressors of p53 in human cancers, are predominantly localized to the nucleus and cytoplasm, respectively. The mechanism by which subcellular localization of Mdmx is regulated remains unclear. In this study, we identify the E3 ligase Peli1 as a major binding partner and regulator of Mdmx in human cells. Peli1 bound Mdmx in vitro and in vivo and promoted high levels of ubiquitination of Mdmx. Peli1-mediated ubiquitination was degradation-independent, promoting cytoplasmic localization of Mdmx, which in turn resulted in p53 activation...
June 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29503445/lymphatic-endothelial-cells-regulate-b-cell-homing-to-lymph-nodes-via-a-nik-dependent-mechanism
#14
Jie Yang, Siya Zhang, Lingyun Zhang, Xiaoping Xie, Hui Wang, Zuliang Jie, Meidi Gu, Jin-Young Yang, Xuhong Cheng, Shao-Cong Sun
B cells home to the lymph nodes (LNs) via high endothelial venules (HEVs) under the guidance of chemokines, particularly CXCL13. However, as CXCL13 is not directly made in HEVs, the molecular mechanism mediating B-cell homing to LNs has remained unclear. We show here that nuclear factor (NF)-κB-inducing kinase (NIK), a kinase mediating activation of the noncanonical NF-κB pathway, functions in lymphatic endothelial cells (LECs) to regulate B-cell homing to LNs. LEC-conditional deletion of NIK in mice did not affect the integrity or global function of lymphatic vessels but caused a severe reduction in the frequency of B cells in LNs...
March 5, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29503440/tbk1-as-a-regulator-of-autoimmunity-and-antitumor-immunity
#15
Jian-Hong Shi, Xiaoping Xie, Shao-Cong Sun
No abstract text is available yet for this article.
March 5, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29463696/genetic-rescue-of-lineage-balanced-blood-cell-production-reveals-a-crucial-role-for-stat3-antiinflammatory-activity-in-hematopoiesis
#16
Huiyuan Zhang, Haiyan S Li, Emily J Hillmer, Yang Zhao, Taylor T Chrisikos, Hongbo Hu, Xiao Wu, Erika J Thompson, Karen Clise-Dwyer, Karen A Millerchip, Yue Wei, Nahum Puebla-Osorio, Saakshi Kaushik, Margarida A Santos, Bin Wang, Guillermo Garcia-Manero, Jing Wang, Shao-Cong Sun, Stephanie S Watowich
Blood cell formation must be appropriately maintained throughout life to provide robust immune function, hemostasis, and oxygen delivery to tissues, and to prevent disorders that result from over- or underproduction of critical lineages. Persistent inflammation deregulates hematopoiesis by damaging hematopoietic stem and progenitor cells (HSPCs), leading to elevated myeloid cell output and eventual bone marrow failure. Nonetheless, antiinflammatory mechanisms that protect the hematopoietic system are understudied...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29228611/proteogenomic-characterization-and-integrative-analysis-of-glioblastoma-multiforme
#17
Ying-Chun Song, Gai-Xia Lu, Hong-Wei Zhang, Xiao-Ming Zhong, Xian-Ling Cong, Shao-Bo Xue, Rui Kong, Dan Li, Zheng-Yan Chang, Xiao-Feng Wang, Yun-Jie Zhang, Ran Sun, Li Chai, Ru-Ting Xie, Ming-Xiang Cai, Ming Sun, Wei-Qing Mao, Hui-Qiong Yang, Yun-Chao Shao, Su-Yun Fan, Ting-Miao Wu, Qing Xia, Zhong-Wei Lv, David A Fu, Yu-Shui Ma
Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158945/nf-%C3%AE%C2%BAb-signaling-in-inflammation
#18
Ting Liu, Lingyun Zhang, Donghyun Joo, Shao-Cong Sun
The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases...
2017: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29078411/peli1-functions-as-a-dual-modulator-of-necroptosis-and-apoptosis-by-regulating-ubiquitination-of-ripk1-and-mrna-levels-of-c-flip
#19
Huibing Wang, Huyan Meng, Xingyan Li, Kezhou Zhu, Kangyun Dong, Adnan K Mookhtiar, Huiting Wei, Ying Li, Shao-Cong Sun, Junying Yuan
Apoptosis and necroptosis are two distinct cell death mechanisms that may be activated in cells on stimulation by TNFα. It is still unclear, however, how apoptosis and necroptosis may be differentially regulated. Here we screened for E3 ubiquitin ligases that could mediate necroptosis. We found that deficiency of Pellino 1 (PELI1), an E3 ubiquitin ligase, blocked necroptosis. We show that PELI1 mediates K63 ubiquitination on K115 of RIPK1 in a kinase-dependent manner during necroptosis. Ubiquitination of RIPK1 by PELI1 promotes the formation of necrosome and execution of necroptosis...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28990243/micrornas-a-novel-potential-biomarker-for-diagnosis-and-therapy-in-patients-with-non-small-cell-lung-cancer
#20
REVIEW
Qun Zhou, Shao-Xin Huang, Feng Zhang, Shu-Jun Li, Cong Liu, Yong-Yong Xi, Liang Wang, Xin Wang, Qi-Qiang He, Cheng-Cao Sun, De-Jia Li
BACKGROUND: Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. AIMS: To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients...
December 2017: Cell Proliferation
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