2014 Vol. 5(2)

Highlight
DSSylation, a novel guide for protein degradation?
Cheng-Xin Gong
2014, 5(2): 91-93. doi: 10.1007/s13238-014-0020-9
Abstract:
Letter
Colonization process of Arabidopsis thaliana roots by a green fluorescent protein-tagged isolate of Verticillium dahliae
Pan Zhao, Yun-Long Zhao, Yun Jin, Tao Zhang, Hui-Shan Guo
2014, 5(2): 94-98. doi: 10.1007/s13238-013-0009-9
Abstract:
Reviews
Genome-scale analysis of demographic history and adaptive selection
Qi Wu, Pingping Zheng, Yibu Hu, Fuwen Wei
2014, 5(2): 99-112. doi: 10.1007/s13238-013-0004-1
Abstract:
One of the main topics in population genetics is identification of adaptive selection among populations. For this purpose, population history should be correctly inferred to evaluate the effect of random drift and exclude it in selection identification. With the rapid progress in genomics in the past decade, vast genomescale variations are available for population genetic analysis, which however requires more sophisticated models to infer species' demographic history and robust methods to detect local adaptation. Here we aim to review what have been achieved in the fields of demographic modeling and selection detection. We summarize their rationales, implementations, and some classical applications. We also propose that some widely-used methods can be improved in both theoretical and practical aspects in near future.
Signaling control of the constitutive androstane receptor (CAR)
Hui Yang, Hongbing Wang
2014, 5(2): 113-123. doi: 10.1007/s13238-013-0013-0
Abstract:
The constitutive androstane receptor (CAR, NR1I3) plays a crucial role in the regulation of drug metabolism, energy homeostasis, and cancer development through modulating the transcription of its numerous target genes. Different from prototypical nuclear receptors, CAR can be activated by either direct ligand binding or ligand-independent (indirect) mechanisms both initiated with nuclear translocation of CAR from the cytoplasm. In comparison to the well-defined ligand-based activation, indirect activation of CAR appears to be exclusively involved in the nuclear translocation through mechanisms yet to be fully understood. Accumulating evidence reveals that without activation, CAR forms a protein complex in the cytoplasm where it can be functionally affected by multiple signaling pathways. In this review, we discuss recent progresses in our understanding of the signaling regulation of CAR nuclear accumulation and activation. We expect that this review will also provide greater insight into the similarity and difference between the mechanisms of direct vs. indirect human CAR activation.
Research articles
DSSylation, a novel protein modification targets proteins induced by oxidative stress, and facilitates their degradation in cells
Yinghao Zhang, Fang-Mei Chang, Jianjun Huang, Jacob J. Junco, Shivani K. Maffi, Hannah I. Pridgen, Gabriel Catano, Hong Dang, Xiang Ding, Fuquan Yang, Dae Joon Kim, Thomas J. Slaga, Rongqiao He, Sung-Jen Wei
2014, 5(2): 124-140. doi: 10.1007/s13238-013-0018-8
Abstract:
Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 (deleted in split hand/split foot 1), an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSS1-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitinproteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.
Murine gammaherpesvirus-68 ORF38 encodes a tegument protein and is packaged into virions during secondary envelopment
Sheng Shen, Haitao Guo, Hongyu Deng
2014, 5(2): 141-150. doi: 10.1007/s13238-013-0005-0
Abstract:
Tegument is the unique structure of a herpesvirion which occupies the space between nucleocapsid and envelope. Accumulating data have indicated that interactions among tegument proteins play a key role in virion morphogenesis. Morphogenesis of gammaherpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) is poorly understood due to the lack of efficient de novo lytic replication in cell culture. Murine gammaherpesvirus-68 (MHV-68) is genetically related to these two human herpesviruses and serves as an effective model to study the lytic replication of gammaherpesviruses. We previously showed that ORF33 of MHV-68 encodes a tegument protein and plays an essential role in virion maturation in the cytoplasm. However, the molecular mechanism of how ORF33 participates in virion morphogenesis has not been elucidated. In this study we demonstrated that ORF38 of MHV-68 is also a tegument protein and is localized to cytoplasmic compartments during both transient transfection and viral infection. Immuno-gold labeling assay showed that ORF38 is only present on virions that have entered the cytoplasmic vesicles, indicating that ORF38 is packaged into virions during secondary envelopment. We further showed that ORF38 co-localizes with ORF33 during viral infection; therefore, the interaction between ORF38 and ORF33 is conserved among herpesviruses. Notably, we found that although ORF33 by itself is distributed in both the nucleus and the cytoplasm, in the presence of ORF38, ORF33 is co-localized to trans-Golgi network (TGN), a site where secondary envelopment takes place.
Crystal structure of E. coli arginyl-tRNA synthetase and ligand binding studies revealed key residues in arginine recognition
Kelei Bi, Yueting Zheng, Feng Gao, Jianshu Dong, Jiangyun Wang, Yi Wang, Weimin Gong
2014, 5(2): 151-159. doi: 10.1007/s13238-013-0012-1
Abstract:
The arginyl-tRNA synthetase (ArgRS) catalyzes the esterification reaction between L-arginine and its cognate tRNAArg. Previously reported structures of ArgRS shed considerable light on the tRNA recognition mechanism, while the aspect of amino acid binding in ArgRS remains largely unexplored. Here we report the first crystal structure of E. coli ArgRS (eArgRS) complexed with L-arginine, and a series of mutational studies using isothermal titration calorimetry (ITC). Combined with previously reported work on ArgRS, our results elucidated the structural and functional roles of a series of important residues in the active site, which furthered our understanding of this unique enzyme.
MicroRNA-29a modulates axon branching by targeting doublecortin in primary neurons
Hanqin Li, Susu Mao, Haitao Wang, Ke Zen, Chenyu Zhang, Liang Li
2014, 5(2): 160-169. doi: 10.1007/s13238-014-0022-7
Abstract:
MicroRNAs (miRNAs) are endogenously expressed small, non-coding transcripts that regulate protein expression. Substantial evidences suggest that miRNAs are enriched in central nervous system, where they are hypothesized to play pivotal roles during neural development. In the present study, we analyzed miRNAs expression in mice cerebral cortex and hippocampus at different developmental stages and found miR-29a increased dramatically at postnatal stages. In addition, we provided strong evidences that miR-29a is enriched in mature neurons both in vitro and in vivo. Further investigation demonstrated that the activation of glutamate receptors induced endogenous miR-29a level in primary neurons. Moreover, we showed that miR-29a directly regulated its target protein Doublecortin (DCX) expression, which further modulated axon branching in primary culture. Together, our results suggested that miR-29a play an important role in neuronal development of mice cerebrum.

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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