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Journal of Molecular Cell Biology

Kunpeng Liu, Lei Zhang, Qiang Zhao, Zhiyao Zhao, Feng Zhi, Yunfei Qin, Jun Cui
NF-κB signaling controls a large set of physiological processes ranging from inflammatory responses to cell death. Its activation is tightly regulated through controlling the activity and stability of multiple signaling components. Here, we identify that NF-κB activation is suppressed by an F-box protein, S-phase kinase associated protein 2 (SKP2). SKP2 deficiency enhanced NF-κB activation as well as the production of inflammatory cytokines. In addition, SKP2 potently blocked the NF-κB activation at the IκB kinase (IKK) level...
February 21, 2018: Journal of Molecular Cell Biology
Yuan Meng, Hongzhi Li, Changwei Liu, Li Zheng, Binghui Shen
No abstract text is available yet for this article.
February 15, 2018: Journal of Molecular Cell Biology
Wenyong Long, Wei Zhao, Bo Ning, Jing Huang, Junjun Chu, Linfeng Li, Qianquan Ma, Changsheng Xing, Helen Y Wang, Qing Liu, Rong-Fu Wang
The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of stemness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Cas9-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. Expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients...
February 14, 2018: Journal of Molecular Cell Biology
Xiangdong Lv, Hao Chen, Shuo Zhang, Zhao Zhang, Chenyu Pan, Yuanxin Xia, Jialin Fan, Wenqing Wu, Yi Lu, Lei Zhang, Hailong Wu, Yun Zhao
The Hedgehog (Hh) signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus (Ci). Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile (1) homeotic (Fsh), a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh,Sex combs extra (Sce) and Polycomb (Pc)...
February 8, 2018: Journal of Molecular Cell Biology
Xue Han, Sai Luo, Guangdun Peng, J Yuyang Lu, Guizhong Cui, Lichao Liu, Pixi Yan, Yafei Yin, Wei Liu, Ran Wang, Zai Chang, Jie Na, Naihe Jing, Xiaohua Shen
No abstract text is available yet for this article.
February 6, 2018: Journal of Molecular Cell Biology
Lixin Cheng, Kwong-Sak Leung
Subcellular localization is pivotal for RNAs and proteins to implement biological functions. The localization diversity of protein interactions has been studied as a crucial feature of proteins, considering the protein-protein interactions take place in various subcellular locations. Nevertheless, the localization diversity of non-coding RNA (ncRNA) target proteins has not been systematically studied, especially its characteristics in cancers. In this study, we provide a new algorithm, non-coding RNA target localization coefficient (ncTALENT), to quantify the target localization diversity of ncRNAs based on the ncRNA-protein interaction and protein subcellular localization data...
January 30, 2018: Journal of Molecular Cell Biology
Benjamin Ravaux, Sophie Favier, Eric Perez, Christine Gourier
Mammalian fertilization involves membrane events -adhesion, fusion, sperm engulfment, membrane block to polyspermy- whose causes remain largely unknown. Recently, specific oscillations of the sperm in contact with the egg were shown to be necessary for fusion. Using a microfluidic chip to impose the venue for the encounter of two gametes allowed real-time observation of the membrane remodelling occurring at the sperm/egg interface. The spatiotemporal mapping of egg CD9 revealed that this protein concentrates at the egg/sperm interface as a result of sperm oscillations, until a CD9-rich platform is nucleated on which fusion immediately takes place...
January 23, 2018: Journal of Molecular Cell Biology
Rachel Xi-Yeen Ho, Rosana D Meyer, Kevin B Chandler, Esma Ersoy, Michael Park, Philip A Bondzie, Nima Rahimi, Huihong Xu, Catherine E Costello, Nader Rahimi
Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins (IUPs) are characterized by the lack of fixed or stable tertiary structure, and are increasingly recognized as an important class of proteins with major roles in signal transduction and transcriptional regulation. In this study, we report the identification and functional characterization of a previously uncharacterized protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a short cytoplasmic domain, it has a large extracellular domain that shares no similarity with known protein sequences...
January 10, 2018: Journal of Molecular Cell Biology
Xin Wang, Congcong Wang, Gang Pei
α-secretase and β-secretase are known to compete for amyloid precursor protein (APP) processing and thus play a vital role in Alzheimer's disease pathogenesis. A disintegrin and metalloproteinase 10 (ADAM10) and β-site APP cleaving enzyme 1 (BACE1) mediate the major activities of α-secretase and β-secretase in brain and share various common substrates. However, whether they function separately or together is poorly understood. Here, we show that ADAM10 and BACE1 co-localize in the neurites of mouse primary neurons...
January 9, 2018: Journal of Molecular Cell Biology
Mengmeng Wu, Zhixiang Lin, Shining Ma, Ting Chen, Rui Jiang, Wing Hung Wong
Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the advanced analysis of the vast volume of existing and anticipated genetic data. Towards this goal, gene-level integrative GWAS analysis with the assumption that genes associated with a phenotype tend to be enriched in biological gene sets or gene networks has recently attracted much attention, due to such advantages as straightforward interpretation, less multiple testing burdens, and robustness across studies...
December 29, 2017: Journal of Molecular Cell Biology
Hai-Bo Xu, Yong-Xin Li, Yan Li, Newton O Otecko, Ya-Ping Zhang, Bingyu Mao, Dong-Dong Wu
New genes are drivers of evolutionary innovation and phenotypic evolution. Expression of new genes in early development raises the possibility that new genes could originate and be recruited for functions in embryonic development, but this remains undocumented. Here, based on temporal gene expression at different developmental stages in Xenopus tropicalis, we found that young protein-coding genes were significantly enriched for expression in developmental stages occurring after the midblastula transition (MBT), and displayed a decreasing trend in abundance in the subsequent stages after MBT...
December 21, 2017: Journal of Molecular Cell Biology
Can Wang, Shihua Zhang
Histone modifications have been widely elucidated to play vital roles in gene regulation and cell identity. The Roadmap Epigenomics Consortium generated a reference catalogue of several key histone modifications across > 100s of human cell types and tissues. Decoding these epigenomes into functional regulatory elements is a challenging task in computational biology. To this end, we adopted a differential chromatin modification analysis framework to comprehensively determine and characterize cell type-specific regulatory elements (CSREs) and their histone modification codes in the human epigenomes of five histone modifications across 127 tissues or cell types...
December 21, 2017: Journal of Molecular Cell Biology
Xing-Ming Zhao, Shan Li
Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP (Hybrid Intelligent approach for identifying directed Signaling Pathways), to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm...
December 21, 2017: Journal of Molecular Cell Biology
Le Zhang, Ying Liu, Mengning Wang, Zhenhai Wu, Na Li, Jinsong Zhang, Chuanwei Yang
Glioma is a complex disease with limited treatment options. Recent advances have identified isocitrate dehydrogenase (IDH) mutations in up to 80% lower grade gliomas (LGG) and in 76% secondary glioblastomas (GBM). IDH mutations are also seen in 10-20% of acute myeloid leukemia (AML). In AML, it was determined that mutations of IDH and other genes involving epigenetic regulations are early events, emerging in the pre-leukemic stem cells (pre-LSCs) stage, whereas mutations in genes propagating oncogenic signal are late events in leukemia...
December 20, 2017: Journal of Molecular Cell Biology
Quan Zheng, Ying Cao, Yalan Chen, Jiqiu Wang, Qiuju Fan, Xian Huang, Yiping Wang, Tianshi Wang, Xiuzhi Wang, Jiao Ma, Jinke Cheng
One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is associated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, we observed overexpression of SUMO-specific protease 2 (Senp2) in adipose tissues during obesity. Adipocyte Senp2 deficiency resulted in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding...
December 20, 2017: Journal of Molecular Cell Biology
Wei Zhao, Peng Tan, Qingyuan Zhu, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y Wang, Rong-Fu Wang
Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo...
December 8, 2017: Journal of Molecular Cell Biology
Kyle K Biggar, Kenneth B Storey
When confronted with severe environmental stress, some animals are able to undergo a substantial reorganization of their cellular environment that enables long-term survival. One molecular mechanism of adaptation that has received considerable attention in recent years has been the action of reversible transcriptome regulation by microRNA. The implementation of new computational and high-throughput experimental approaches have started to uncover the vital contributions of microRNA towards stress adaptation...
December 1, 2017: Journal of Molecular Cell Biology
Luonan Chen
No abstract text is available yet for this article.
December 1, 2017: Journal of Molecular Cell Biology
Lei Duan, Ricardo E Perez, Ling Chen, Lothar A Blatter, Carl G Maki
Nutlin-3a is a MDM2 antagonist and preclinical drug that activates p53. Cells with MDM2 gene amplification are especially prone to Nutlin-3a-induced apoptosis, though the basis for this is unclear. Glucose metabolism can inhibit apoptosis in response to Nutlin-3a through mechanisms that are incompletely understood. Glucose metabolism through the pentose phosphate pathway (PPP) produces NADPH that can protect cells from potentially lethal reactive oxygen species (ROS). We compared apoptosis and glucose metabolism in cancer cells with and without MDM2 gene amplification treated with Nutlin-3a...
November 27, 2017: Journal of Molecular Cell Biology
Enas R Abu-Zhayia, Samah W Awwad, Bella Ben-Oz, Hanan Khoury-Haddad, Nabieh Ayoub
Cells have evolved DNA damage response (DDR) to repair DNA lesions and thus preserving genomic stability and impeding carcinogenesis. DNA damage induction is accompanied by transient transcription repression. Here, we describe a previously unrecognized role of chromodomain Y-like (CDYL1) protein in fortifying double-strand break (DSB)-induced transcription repression and repair. We showed that CDYL1 is rapidly recruited to damaged euchromatic regions in a poly [ADP-ribose] polymerase 1 (PARP1)-dependent, but ataxia telangiectasia mutated (ATM)-independent, manner...
November 21, 2017: Journal of Molecular Cell Biology
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