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Journal of Molecular Cell Biology

Qin Chen, Peiliang Shi, Yufang Wang, Dayuan Zou, Xiuwen Wu, Dingyu Wang, Qiongyuan Hu, Yujie Zou, Zan Huang, Jianan Ren, Zhaoyu Lin, Xiang Gao
Gasdermin B (GSDMB) has been reported to be associated with immune diseases in humans, but the detailed molecular mechanisms remain unsolved. The N-terminus of GSDMB by itself, unlike other gasdermin family proteins, does not induce cell death. Here, we show that GSDMB is highly expressed in the leukocytes of septic shock patients, which is associated with increased release of the GSDMD N-terminus. GSDMB expression and the accumulation of the N-terminal fragment of GSDMD are induced by the activation of the non-canonical pyroptosis pathway in a human monocyte cell line...
October 15, 2018: Journal of Molecular Cell Biology
Haibo Gao, Rui Gao, Linfeng Zhang, Wenchao Xiu, Ruge Zang, Hong Wang, Yong Zhang, Yawei Gao, Jiayu Chen, Shaorong Gao
Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essential insights into the molecular mechanisms controlling the placental development can be gained by using TSCs as the cell model. Esrrb is a transcription factor that has been shown to play pivotal roles in both embryonic stem cell (ESC) and TSC, but the precise mechanism whereby Esrrb regulates TSC-specific transcriptome during differentiation and reprogramming is still largely unknown...
October 9, 2018: Journal of Molecular Cell Biology
Xiaoli Sun, Huizhen Lv, Peng Zhao, Jinlong He, Qinghua Cui, Minxin Wei, Shiqing Feng, Yi Zhu
Endothelial NO synthase (eNOS) expression is regulated by a number of transcriptional and post-transcriptional mechanisms, but the effects of competing endogenous RNAs (ceRNAs) on eNOS mRNA and the underlying mechanisms are still unknown. Our bioinformatic analysis revealed three highly expressed eNOS-targeting miRNAs (miR-15b, miR-16, and miR-30b) in human endothelial cells (ECs). Among the 1103 mRNA targets of these three miRNAs, 15 mRNAs share a common disease association with eNOS. Gene expression and correlation analysis in patients with cardiovascular diseases identified insulin receptor substrate 2 (IRS2) as the most correlated eNOS-ceRNA...
October 8, 2018: Journal of Molecular Cell Biology
Konstantinos Karakostis, Sivakumar Vadivel Gnanasundram, Ignacio López, Aikaterini Thermou, Lixiao Wang, Karin Nylander, Vanesa Olivares-Illana, Robin Fåhraeus
p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners. The hierarchical order and subcellular location of these events are still poorly understood. The activation of p53 during the DNA damage response (DDR) requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53. This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis...
September 24, 2018: Journal of Molecular Cell Biology
Alex R Straughn, Sajedah M Hindi, Gunagyan Xiong, Ashok Kumar
Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate, differentiate, and eventually fuse with injured myofibers. However, the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood. While IKKβ-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass, its regulation of satellite cell function during muscle regeneration remains less understood. Here, we report that canonical NF-κB signaling is induced in skeletal muscle upon injury...
September 19, 2018: Journal of Molecular Cell Biology
Yong Zhang, Yuping Zhang, Kun Sun, Ziyi Meng, Ligong Chen
The prevalence of metabolic diseases is growing worldwide. Accumulating evidence suggests that solute carrier (SLC) transporters contribute to the aetiology of various metabolic diseases. Consistent with metabolic characteristics, the top 5 organs in which SLC transporters are highly expressed are the kidney, brain, liver, gut, and heart. Our long-term research goals are to understand the molecular mechanisms of important SLC transporter-mediated physiological processes and their potentials as drug targets...
September 18, 2018: Journal of Molecular Cell Biology
María I Calvo-Sánchez, Sandra Fernández-Martos, Elisa Carrasco, Gema Moreno-Bueno, Carmelo Bernabéu, Miguel Quintanilla, Jesús Espada
The hair follicle is a biological oscillator that alternates growth, regression, and rest phases driven by the sequential activation of the proliferation/differentiation programs of resident stem cell populations. The activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling, while regression and resting phases are mainly regulated by Tgf-β/Bmp/Smad activity. A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling pathways...
September 18, 2018: Journal of Molecular Cell Biology
Chunhua Tang, Minjie Ni, Shengsong Xie, Yao Zhang, Chaobao Zhang, Zimei Ni, Chen Chu, Ligang Wu, Yuchuan Zhou, Yonglian Zhang
DICER1 is a key enzyme responsible for the maturation of microRNAs. Recent evidences suggested that DICER1 and microRNAs expressed in epididymis were involved in the control of male fertility. However, the exact mechanism remains to be elucidated. Here, we created a mouse line by targeted disruption of Dicer1 gene in the principal cells of distal caput epididymis. Our data indicated that a set of β-defensin genes were downregulated by DICER1 rather than by microRNAs. Moreover, DICER1 was significantly enriched in the promoter of β-defensin gene and controlled transcription...
September 12, 2018: Journal of Molecular Cell Biology
Qianqian Cai, Yuanyuan Liu, Ping Zhu, Chunlang Kang, Heyang Xu, Bing Qi, Rong Wang, Yiwei Dong, Xing Zhong Wu
Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin αV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin αV and SIN3B expressions in HCC patients and tumor cell lines with different metastatic potentials. Overexpression of SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed when integrin αV expression was silenced...
September 12, 2018: Journal of Molecular Cell Biology
Xiaoli Xu, Rongyi Shi, Li Zheng, Zhigang Guo, Liangyan Wang, Mian Zhou, Ye Zhao, Bing Tian, Khue Truong, Yuan Chen, Binghui Shen, Yuejin Hua, Hong Xu
Human flap endonuclease 1 (FEN1) is a structure-specific, multi-functional endonuclease essential for DNA replication and repair. We and others have shown that during DNA replication, FEN1 processes Okazaki fragments via its interaction with the proliferating cell nuclear antigen (PCNA). Alternatively, in response to DNA damage, FEN1 interacts with the PCNA-like Rad9-Rad1-Hus1 complex instead of PCNA to engage in DNA repair activities, such as homology-directed repair of stalled DNA replication forks. However, it is unclear how FEN1 is able to switch between these interactions and its roles in DNA replication and DNA repair...
September 3, 2018: Journal of Molecular Cell Biology
Chengfei Zhang, Yan Yan, Hongwang He, Li Wang, Na Zhang, Jie Zhang, Hongjun Huang, Nannan Wu, Hua Ren, Min Qian, Mingyao Liu, Bing Du
Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y13 and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y13, as a typical interferon-stimulated gene (ISG), is induced together with extracellular ADP during viral infection...
August 22, 2018: Journal of Molecular Cell Biology
Xiaotong Wu, Weimin Shen, Bingjie Zhang, Anming Meng
Oocytes, the irreplaceable gametes for generating a new organism, are matured in the ovary of living female animals. It is unknown whether any genetic manipulations can be applied to immature oocytes inside the living ovaries. As a proof-of-concept, we here demonstrate genetic amendments of zebrafish immature oocytes within the ovary. Oocyte microinjection in situ (OMIS) stimulates tissue repair responses, but some of microinjected immature oocytes are matured, ovulated and fertilizable. By OMIS-mediated Cas9 approach, ntla and gata5 loci of oocytes arrested at prophase I of meiosis are successfully edited before fertilization...
July 28, 2018: Journal of Molecular Cell Biology
Yirong Zhang, Yawen Chen, Jianqun Zheng, Juan Wang, Shichao Duan, Wei Zhang, Xiumin Yan, Xueliang Zhu
Motile cilia and flagella are microtubule-based organelles important for cell locomotion and extracellular liquid flow through beating. Although axomenal dyneins that drive ciliary beat have been extensively studied in unicellular Chlamydomonas, to what extent such knowledge can be applied to vertebrate is poorly known. In Chlamydomonas, Dynein-f controls flagellar waveforms but is dispensable for beating. The flagellar assembly of its heavy chains (HCs) requires its intermediate chain (IC) IC140 but not IC138...
July 28, 2018: Journal of Molecular Cell Biology
Sanhong Liu, Zifeng Wang, Zukai Liu, Shuo Shi, Zhaoran Zhang, Jiawei Zhang, Haifan Lin
Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targeted therapies. Wnt/β-catenin signaling is hyperactivated in TNBC, which promotes the progression of TNBC. However, the molecular mechanism of Wnt/β-catenin activation in TNBC remains unknown...
July 25, 2018: Journal of Molecular Cell Biology
Hua Lu
No abstract text is available yet for this article.
August 1, 2018: Journal of Molecular Cell Biology
Mary Ellen Molloy, Monika Lewinska, Amanda K Williamson, Thanh Thao Nguyen, Gamze Kuser-Abali, Lu Gong, Jiawei Yan, John B Little, Pier Paolo Pandolfi, Zhi-Min Yuan
ZBTB7A, a member of the POZ/BTB and Krüppel (POK) family of transcription factors, has been shown to have a context-dependent role in cancer development and progression. The role of ZBTB7A in estrogen receptor alpha (ERα)-positive breast cancer is largely unknown. Approximately 70% of breast cancers are classified as ERα-positive. ERα carries out the biological effects of estrogen and its expression level dictates response to endocrine therapies and prognosis for breast cancer patients. In this study, we find that ZBTB7A transcriptionally regulates ERα expression in ERα-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ERα...
August 1, 2018: Journal of Molecular Cell Biology
Wei Zhao, Qingyuan Zhu, Peng Tan, 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...
August 1, 2018: 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...
August 1, 2018: Journal of Molecular Cell Biology
Limin Liu, Peng Zhang, Ming Bai, Lijie He, Lei Zhang, Ting Liu, Zhen Yang, Menglu Duan, Minna Liu, Baojian Liu, Rui Du, Qi Qian, Shiren Sun
Hypoxia plays an important role in the genesis and progression of renal fibrosis. The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting...
July 18, 2018: Journal of Molecular Cell Biology
Huiyan Sun, Chi Zhang, Sha Cao, Tao Sheng, Ning Dong, Ying Xu
We present a computational study of tissue transcriptomic data of 14 cancer types to address: what may drive cancer cell division? Our analyses point to that persistent disruption of the intracellular pH by Fenton reactions may be at the root of cancer development. Specifically, we have statistically demonstrated that Fenton reactions take place in cancer cytosol and mitochondria across all the 14 cancer types, based on cancer tissue gene-expression data integrated via the Michaelis-Menten equation. In addition, we have shown that (i) Fenton reactions in cytosol of the disease cells will continuously increase their pH, to which the cells respond by generating net protons to keep the pH stable through a combination of synthesizing glycolytic ATPs and consuming them by nucleotide syntheses, which may drive cell division to rid of the continuously synthesized nucleotides; and (ii) Fenton reactions in mitochondria give rise to novel ways for ATP synthesis with electrons ultimately coming from H2O2, largely originated from immune cells...
July 16, 2018: Journal of Molecular Cell Biology
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