2017 Vol. 8(4)

Nathaniel Gist Gee's contribution to biology in modern China
Lei Fu
2017, 8(4): 237-239. doi: 10.1007/s13238-016-0318-x
N4 DNA recognition by STAT6: structural and functional implications
Xiang Zhou, Zhengfan Jiang
2017, 8(4): 240-241. doi: 10.1007/s13238-017-0380-z
Transcriptional regulators dictate innate lymphoid cell fates
Chao Zhong, Jinfang Zhu
2017, 8(4): 242-254. doi: 10.1007/s13238-017-0369-7
Research on innate lymphoid cells (ILC) has recently been a fast paced topic of immunological research. As ILCs are able to produce signature Th cytokine, ILCs have garnered considerable attention and have been described to represent the innate counterpart of the CD4+ T helper (Th) cells. The development and function of ILCs are precisely regulated by a network of crucial transcription factors, which are also involved in the development or differentiation of conventional natural killer (cNK) cells and T cells. In this review, we will summarize the key transcriptional regulators and their functions through each phases of ILC development. With the phase of ILC lineage commitment, we will focus in particular on the roles of the transcription regulators Id2 and GATA-3, which in collaboration with other transcriptional factors, are critically involved in the generation of ILC fate determined progenitors. Once an ILC lineage has been established, several other transcription factors are required for the specification and functional regulation of distinct mature ILC subsets. Thus, a comprehensive understanding of the interactions and regulatory mechanisms mediated by these transcription factors will help us to further understand how ILCs exert their helper-like functions and bridge the innate and adaptive immunity.
Reversible phosphorylation of the 26S proteasome
Xing Guo, Xiuliang Huang, Mark J. Chen
2017, 8(4): 255-272. doi: 10.1007/s13238-017-0382-x
The 26S proteasome at the center of the ubiquitinproteasome system (UPS) is essential for virtually all cellular processes of eukaryotes. A common misconception about the proteasome is that, once made, it remains as a static and uniform complex with spontaneous and constitutive activity for protein degradation. Recent discoveries have provided compelling evidence to support the exact opposite insomuch as the 26S proteasome undergoes dynamic and reversible phosphorylation under a variety of physiopathological conditions. In this review, we summarize the history and current understanding of proteasome phosphorylation, and advocate the idea of targeting proteasome kinases/phosphatases as a new strategy for clinical interventions of several human diseases.
Research articles
Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury
Yuewen Tang, Lin Cheng
2017, 8(4): 273-283. doi: 10.1007/s13238-017-0373-y
Tissue damage induces cells into reprogramming-like cellular state, which contributes to tissue regeneration. However, whether factors promoting the cell reprogramming favor tissue regeneration remains elusive. Here we identified combination of small chemical compounds including drug cocktails robustly promoting in vitro cell reprogramming. We then administrated the drug cocktails to mice with acute liver injuries induced by partial hepatectomy or toxic treatment. Our results demonstrated that the drug cocktails which promoted cell reprogramming in vitro improved liver regeneration and hepatic function in vivo after acute injuries. The underlying mechanism could be that expression of pluripotent genes activated after injury is further upregulated by drug cocktails. Thus our study offers proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose.
Functional characterization of human equilibrative nucleoside transporter 1
Weiyun Huang, Xin Zeng, Yigong Shi, Minhao Liu
2017, 8(4): 284-295. doi: 10.1007/s13238-016-0350-x
Equilibrative nucleoside transporters (ENTs), which facilitate cross-membrane transport of nucleosides and nucleoside-derived drugs, play an important role in the salvage pathways of nucleotide synthesis, cancer chemotherapy, and treatment for virus infections. Functional characterization of ENTs at the molecular level remains technically challenging and hence scant. In this study, we report successful purification and biochemical characterization of human equilibrative nucleoside transporter 1 (hENT1) in vitro. The HEK293Fderived, recombinant hENT1 is homogenous and functionally active in proteoliposome-based counter flow assays. hENT1 transports the substrate adenosine with a Km of 215±34 μmol/L and a Vmax of 578±23.4 nmol mg-1 min-1. Adenosine uptake by hENT1 is competitively inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), nucleosides, deoxynucleosides, and nucleoside-derived anti-cancer and anti-viral drugs. Binding of hENT1 to adenosine, deoxyadenosine, and adenine by isothermal titration calorimetry is in general agreement with results of the competitive inhibition assays. These results validate hENT1 as a bona fide target for potential drug target and serve as a useful basis for future biophysical and structural studies.
PML-RARA mutations confer varying arsenic trioxide resistance
Dong-Mei Bai, Xiao-Feng Zheng
2017, 8(4): 296-301. doi: 10.1007/s13238-016-0356-4
Identification of microRNA expression profiles in the gill, intestine and hepatic caecum of Branchiostoma belcheri
Xin Liao, Liu Yang, Xi Chen, Junyuan Chen
2017, 8(4): 302-307. doi: 10.1007/s13238-016-0365-3
Structural insights into glutathione-mediated activation of the master regulator PrfA in Listeria monocytogenes
Yong Wang, Han Feng, Yalan Zhu, Pu Gao
2017, 8(4): 308-312. doi: 10.1007/s13238-017-0390-x
Jiaxiang Shao, Xiao Yang, Tengyuan Liu, Tingting Zhang, Qian Reuben Xie, Weiliang Xia
2017, 8(4): 313-313. doi: 10.1007/s13238-017-0370-1

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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