2014 Vol. 5(10)

Chih Tu: A pioneer of Xinjiang's agricultural science
Fang Zhang
2014, 5(10): 725-727. doi: 10.1007/s13238-014-0096-2
Insights into battles between Mycobacterium tuberculosis and macrophages
Guanghua Xu, Jing Wang, George Fu Gao, Cui Hua Liu
2014, 5(10): 728-736. doi: 10.1007/s13238-014-0077-5
As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years.The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs).Inaddition,Vitamin Dreceptor(VDR) and VitaminD-1-hydroxy lase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses.The signaling pathways that involve TNF,type I IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes.
Mitochondria-mediated apoptosis in mammals
Shunbin Xiong, Tianyang Mu, Guowen Wang, Xuejun Jiang
2014, 5(10): 737-749. doi: 10.1007/s13238-014-0089-1
The mitochondria-mediated caspase activation pathway is a major apoptotic pathway characterized by mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP is regulated by the Bcl-2 family of proteins. This pathway plays important roles not only in normal development, maintenance of tissue homeostasis and the regulation of immune system, but also in human diseases such as immune disorders, neurodegeneration and cancer. In the past decades the molecular basis of this pathway and the regulatory mechanism have been comprehensively studied, yet a great deal of new evidence indicates that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions. Thus, many unsolved questions and new challenges are still remaining. Furthermore, the dysfunction of this pathway involved in cancer development is obvious, and targeting the pathway as a therapeutic strategy has been extensively explored, but the efficacy of the targeted therapies is still under development. In this review we will discuss the mitochondria-mediated apoptosis pathway and its physiological roles and therapeutic implications.
Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control
Caiguo Zhang
2014, 5(10): 750-760. doi: 10.1007/s13238-014-0083-7
Eukaryotic cells contain numerous iron-requiring proteins such as iron-sulfur (Fe-S) cluster proteins, hemoproteins and ribonucleotide reductases (RNRs). These proteins utilize iron as a cofactor and perform key roles in DNA replication, DNA repair, metabolic catalysis, iron regulation and cell cycle progression. Disruption of iron homeostasis always impairs the functions of these ironrequiring proteins and is genetically associated with diseases characterized by DNA repair defects in mammals. Organisms have evolved multi-layered mechanisms to regulate iron balance to ensure genome stability and cell development. This review briefly provides current perspectives on iron homeostasis in yeast and mammals, and mainly summarizes the most recent understandings on iron-requiring protein functions involved in DNA stability maintenance and cell cycle control.
Research articles
Gluconate 5-dehydrogenase (Ga5DH) participates in Streptococcus suis cell division
Zhongyu Shi, Chunling Xuan, Huiming Han, Xia Cheng, Jundong Wang, Youjun Feng, Swaminath Srinivas, Guangwen Lu, George F. Gao
2014, 5(10): 761-769. doi: 10.1007/s13238-014-0074-8
Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified.Here,we report the requirement of gluconate 5-dehydrogenase (Ga5DH) in cell division of the zoonotic pathogen Streptococcus suis. Ga5DH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division.The deletion of Ga5DH in S. suisresulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the consequence of Ga5DH deprivation in S. suis causing FtsZ delocalization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that Ga5DH may function to prevent the formation of ectopic Z rings during S. suis cell division.
Analysis of the p53/CEP-1 regulated non-coding transcriptome in C. elegans by an NSR-seq strategy
Derong Xu, Guifeng Wei, Ping Lu, Jianjun Luo, Xiaomin Chen, Geir Skogerbø, Runsheng Chen
2014, 5(10): 770-782. doi: 10.1007/s13238-014-0071-y
In recent years, large numbers of non-coding RNAs (ncRNAs) have been identified in C. elegans but their functions are still not well studied. In C. elegans, CEP-1 is the sole homolog of the p53 family of genes. In order to obtain transcription profiles of ncRNAs regulated by CEP-1 under normal and UV stress ed conditions, we applied the ‘not-sorandom’ hexamers priming strategy to RNA sequencing in C. elegans, This NSR-seq strategy efficiently depleted rRNA transcripts from the samples and showed high technical replicability. We identified more than 1,000 ncRNAs whose apparent expression was repressed by CEP-1, while around 200 were activated. Around 40% of the CEP-1 activated ncRNAs promoters contain a putative CEP-1-binding site. CEP-1 regulated ncRNAs were frequently clustered and concentrated on the X chromosome. These results indicate that numerous ncRNAs are involved in CEP-1 transcriptional network and that these are especially enriched on the X chromosome in C. elegans.
Alterations of the Ca2+ signaling pathway in pancreatic beta-cells isolated from db/db mice
Kuo Liang, Wen Du, Jingze Lu, Fei Li, Lu Yang, Yanhong Xue, Bertil Hille, Liangyi Chen
2014, 5(10): 783-794. doi: 10.1007/s13238-014-0075-7
Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2+-dependent manner. In diabetic animal models, different aspects of the calcium signaling pathway in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca2+ ([Ca2+]i) via Ca2+ influx, Ca2+ mobilization from endoplasmic reticulum (ER) calcium stores, and the removal of Ca2+ via multiple mechanisms in beta-cells from both diabetic db/db mice and nondiabetic C57BL/6J mice. We refined our previous quantitative model to describe the slow[Ca2+]i recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump, SERCA2 and SERCA3, were severely down-regulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduction in the Ca2+ concentration in the ER, a compensatory up-regulation of the plasma membrane Na+/Ca2+ exchanger (NCX) and a reduction in depolarizationevoked Ca2+ influx. As a result, the patterns of glucosestillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic bimulated calcium osceta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.
Phosphoregulation of the dimerization and functions of end-binding protein 1
Jie Chen, Youguang Luo, Lixin Li, Jie Ran, Xincheng Wang, Siqi Gao, Min Liu, Dengwen Li, Wenqing Shui, Jun Zhou
2014, 5(10): 795-799. doi: 10.1007/s13238-014-0081-9
The specific and rapid labeling of cell surface proteins with recombinant FKBP-fused fluorescent proteins
Xi Zhang, Yongqiang Deng, Hao Chang, Chen Ji, Mingshu Zhang, Jianxin Peng, Tao Xu, Pingyong Xu
2014, 5(10): 800-803. doi: 10.1007/s13238-014-0090-8

Current Issue

March, 2019

Volume 10, Issue 3

Pages 157-233

About the cover

Metastasis is the leading cause of human cancer deaths.Unfortunately, no approved drugs are available for antimetastatic treatment. In this study, high-throughputsequencing-based high-throughput screening (HTS2) anda breast cancer lung metastasis (BCLM)-associated genesignature were combined to discover anti-metastatic drugs.After screening of thousands of compounds, Shao et al.identifed Ponatinib as a BCLM inhibitor. Ponatinib signifcantlyinhibited the migration and mammosphere formation of breastcancer cells in vitro and blocked BCLM in multiple mousemodels. This study may facilitate the therapeutic treatment ofBCLM as well as other metastases.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang Beijing 100101, China

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