2011 Vol. 2(10)

News and views
Youyou Tu honored by the Lasker award
Xiaoxue Zhang
2011, 2(10): 773-773. doi: 10.1007/s13238-011-1111-5
Systematic temperature signaling regulates behavior plasticity
Yun Li
2011, 2(10): 774-775. doi: 10.1007/s13238-011-1109-z
Genetic engineering and enzyme research in lignocellulosic ethanol production
Elizabeth Jane Ashforth
2011, 2(10): 776-777. doi: 10.1007/s13238-011-1108-0
Romance of the three kingdoms: RORgammat allies with HIF1alpha against FoxP3 in regulating T cell metabolism and differentiation
Andy Tsun, Zuojia Chen, Bin Li
2011, 2(10): 778-781. doi: 10.1007/s13238-011-1114-2
Innovator of in vitro virus culture—Dr. Chen-Hsiang Huang
Guangsheng Cheng
2011, 2(10): 782-783. doi: 10.1007/s13238-011-1110-6
Role of plant autophagy in stress response
Shaojie Han, Bingjie Yu, Yan Wang, Yule Liu
2011, 2(10): 784-791. doi: 10.1007/s13238-011-1104-4
Autophagy is a conserved pathway for the bulk degradation of cytoplasmic components in all eukaryotes. This process plays a critical role in the adaptation of plants to drastic changing environmental stresses such as starvation, oxidative stress, drought, salt, and pathogen invasion. This paper summarizes the current knowledge about the mechanism and roles of plant autophagy in various plant stress responses.
Mechanism and methods to induce pluripotency
Peizhe Wang, Jie Na
2011, 2(10): 792-799. doi: 10.1007/s13238-011-1107-1
Pluripotent stem cells are able to self-renew indefinitely and differentiate into all types of cells in the body. They can thus be an inexhaustible source for future cell transplantation therapy to treat degenerative diseases which currently have no cure. However, non-autologous cells will cause immune rejection. Induced pluripotent stem cell (iPSC) technology can convert somatic cells to the pluripotent state, and therefore offers a solution to this problem. Since the first generation of iPSCs, there has been an explosion of relevant research, from which we have learned much about the genetic networks and epigenetic landscape of pluripotency, as well as how to manipulate genes, epigenetics, and microRNAs to obtain iPSCs. In this review, we focus on the mechanism of cellular reprogramming and current methods to induce pluripotency. We also highlight new problems emerging from iPSCs. Better understanding of the fundamental mechanisms underlying pluripotenty and refining the methodology of iPSC generation will have a significant impact on future development of regenerative medicine.
Expanding neurotransmitters in the hypothalamic neurocircuitry for energy balance regulation
Yuanzhong Xu, Qingchun Tong
2011, 2(10): 800-813. doi: 10.1007/s13238-011-1112-4
The current epidemic of obesity and its associated metabolic syndromes impose unprecedented challenges to our society. Despite intensive research on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of the leptin neural pathway in the hypothalamus in the regulation of body weight homeostasis. Important hypothalamic neuropeptides have been identified as critical neurotransmitters from leptin-sensitive neurons to mediate leptin action. Recent research advance has significantly expanded the list of neurotransmitters involved in body weight-regulating neural pathways, including fast-acting neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. Given the limited knowledge on the leptin neural pathway for body weight homeostasis, understanding the function of neurotransmitters released from key neurons for energy balance regulation is essential for delineating leptin neural pathway and eventually for designing effective therapeutic drugs against the obesity epidemic.
Research articles
Crystal structure of human Gadd45 reveals an active dimer
Wenzheng Zhang, Sheng Fu, Xuefeng Liu, Xuelian Zhao, Wenchi Zhang, Wei Peng, Congying Wu, Yuanyuan Li, Xuemei Li, Mark Bartlam, Zong-Hao Zeng, Qimin Zhan, Zihe Rao
2011, 2(10): 814-826. doi: 10.1007/s13238-011-1090-6
The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45, revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45 identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that:(1) dimerization of Gadd45 is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.
Structural insight into substrate specificity of human intestinal maltase-glucoamylase
Limei Ren, Xiaohong Qin, Xiaofang Cao, Lele Wang, Fang Bai, Gang Bai, Yuequan Shen
2011, 2(10): 827-836. doi: 10.1007/s13238-011-1105-3
Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino-and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 Å, and in complex with its inhibitor acarbose at a resolution of 2.9 Å. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alphaglucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.
Programmed cell death may act as a surveillance mechanism to safeguard male gametophyte development in Arabidopsis
Jian Zhang, Chong Teng, Yan Liang
2011, 2(10): 837-844. doi: 10.1007/s13238-011-1102-6
Programmed cell death (PCD) plays an important role in plant growth and development as well as in stress responses. During male gametophyte development, it has been proposed that PCD may act as a cellular surveillance mechanism to ensure successful progression of male gametogenesis, and this suicide protective machinery is repressed under favorable growth conditions. However, the regulatory mechanism of male gametophyte-specific PCD remains unknown. Here, we report the use of a TdT-mediated dUTP nick-end labelingbased strategy for genetic screening of Arabidopsis mutants that present PCD phenotype during male gametophyte development. By using this approach, we identified 12 mutants, designated as pcd in male gametogenesis (pig). pig mutants are defective at various stages of male gametophyte development, among which nine pig mutants show a microspore-specific PCD phenotype occurring mainly around pollen mitosis I or the bicellular stage. The PIG1 gene was identified by map-based cloning, and was found to be identical to ATAXIA TELANGIECTASIA MUTATED (ATM), a highly conserved gene in eukaryotes and a key regulator of the DNA damage response. Our results suggest that PCD may act as a general mechanism to safeguard the entire process of male gametophyte development.
SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion
Xiaolei Liu, Biyan Duan, Zhaokang Cheng, Xiaohua Jia, Lina Mao, Hao Fu, Yongzhe Che, Lailiang Ou, Lin Liu, Deling Kong
2011, 2(10): 845-854. doi: 10.1007/s13238-011-1097-z
Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H2O2 for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4. We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.

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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