2017 Vol. 8, No. 3

Jilun Li and his profound impact on theoretical and applied agricultural microbiology
Chengbo Rong, Yu Liu, Ying Wen
2017, 8(3): 159-161. doi: 10.1007/s13238-016-0359-1
Zika virus in the testes: should we be worried?
Gary Wong, Shihua Li, Lei Liu, Yingxia Liu, Yuhai Bi
2017, 8(3): 162-164. doi: 10.1007/s13238-016-0357-3
RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway
Saurabh Chattopadhyay, Ganes C. Sen
2017, 8(3): 165-168. doi: 10.1007/s13238-016-0334-x
The innate immune response is the first line of host defense to eliminate viral infection. Pattern recognition receptors in the cytosol, such as RIG-I-like receptors (RLR) and Nod-like receptors (NLR), and membrane bound Toll like receptors (TLR) detect viral infection and initiate transcription of a cohort of antiviral genes, including interferon (IFN) and interferon stimulated genes (ISGs), which ultimately block viral replication. Another mechanism to reduce viral spread is through RIPA, the RLR-induced IRF3-mediated pathway of apoptosis, which causes infected cells to undergo premature death. The transcription factor IRF3 can mediate cellular antiviral responses by both inducing antiviral genes and triggering apoptosis through the activation of RIPA. The mechanism of IRF3 activation in RIPA is distinct from that of transcriptional activation; it requires linear polyubiquitination of specific lysine residues of IRF3. Using RIPA-active, but transcriptionally inactive, IRF3 mutants, it was shown that RIPA can prevent viral replication and pathogenesis in mice.
Understand spiciness: mechanism of TRPV1 channel activation by capsaicin
Fan Yang, Jie Zheng
2017, 8(3): 169-177. doi: 10.1007/s13238-016-0353-7
Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge:capsaicin binds to a pocket formed by the channel's transmembrane segments, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-andcontact" with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1.
Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance
Yingjiao Xue, Shenda Hou, Hongbin Ji, Xiangkun Han
2017, 8(3): 178-190. doi: 10.1007/s13238-016-0330-1
Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
Research articles
IL-25 blockade inhibits metastasis in breast cancer
Zhujun Jiang, Jingtao Chen, Xuemei Du, Hang Cheng, Xiaohu Wang, Chen Dong
2017, 8(3): 191-201. doi: 10.1007/s13238-016-0345-7
Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumorinfiltrating CD4+ T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
E3 ligase UHRF2 stabilizes the acetyltransferase TIP60 and regulates H3K9ac and H3K14ac via RING finger domain
Shengyuan Zeng, Yangyang Wang, Ting Zhang, Lu Bai, Yalan Wang, Changzhu Duan
2017, 8(3): 202-218. doi: 10.1007/s13238-016-0324-z
UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination. However, TIP60 is destabilized in cancer cells. Depletion or inhibition of TIP60 disrupts the regulatory relationship between UHRF2, H3K9ac and H3K14ac. In summary, the findings suggest that UHRF2 mediated the post-translational modification of histones and the initiation and progression of cancer.
Electron microscopy studies of the coronavirus ribonucleoprotein complex
Miao Gui, Xin Liu, Deyin Guo, Zhen Zhang, Chang-Cheng Yin, Yu Chen, Ye Xiang
2017, 8(3): 219-224. doi: 10.1007/s13238-016-0352-8
The chimeric Japanese encephalitis/Dengue 2 virus protects mice from challenge by both dengue virus and JEV virulent virus
Jian Yang, Huiqiang Yang, Zhushi Li, Hua Lin, Yu Zhao, Wei Wang, Shuai Tan, Xianwu Zeng, Yuhua Li
2017, 8(3): 225-229. doi: 10.1007/s13238-016-0363-5
Targeted disruption of Noc4l leads to preimplantation embryonic lethality in mice
Yongli Qin, Haifeng Li, Lina Jia, Jinghua Yan, George Fu Gao, Xiangdong Li
2017, 8(3): 230-235. doi: 10.1007/s13238-016-0335-9