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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
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
Daniëlle R J Verboogen, Natalia H Revelo, Martin Ter Beest, Geert van den Bogaart
Cells producing cytokines often express the receptor for the same cytokine, which makes them prone to autocrine signaling. How cytokine release and signaling are regulated in the same cell is not understood. In this study, we demonstrate that signaling by exogenous and self-synthesized inflammatory cytokine interleukin-6 (IL-6) within endosomal compartments acts as a cellular brake that limits synthesis of IL-6. Our data show that IL-6 is internalized by dendritic cells and signals from endosomal compartments containing the IL-6 receptor...
July 16, 2018: Journal of Molecular Cell Biology
Saima Akram, Fengrui Yang, Junying Li, Gregory Adams, Yingying Liu, Xiaoxuan Zhuang, Lingluo Chu, Xu Liu, Nerimah Emmett, Winston Thompson, McKay Mullen, Saravana Muthusamy, Wenwen Wang, Fei Mo, Xing Liu
Heterochromatin protein 1α (HP1α) regulates chromatin specification and plasticity during cell fate decision. Different structural determinants account for HP1α localization and function during cell division cycle. Our earlier study showed that centromeric localization of HP1α depends on the epigenetic mark H3K9me3 in interphase, while its centromeric location in mitosis relies on uncharacterized PXVXL-containing factors. Here, we identified a PXVXL-containing protein, ligand-dependent nuclear receptor-interacting factor 1 (LRIF1), which recruits HP1α to the centromere of mitotic chromosomes and its interaction with HP1α is essential for accurate chromosome segregation during mitosis...
July 16, 2018: Journal of Molecular Cell Biology
Gabriel Heras, Arvind Venkat Namuduri, Leonardo Traini, Ganna Shevchenko, Alexander Falk, Sara Bergström Lind, Jia Mi, Geng Tian, Stefano Gastaldello
The Muscle RING-finger protein-1 (MuRF1) is an E3 ubiquitin ligase expressed in skeletal and cardiac muscle tissues and it plays important roles in muscle remodeling. Upregulation of MuRF1 gene transcription participates in skeletal muscle atrophy, on contrary downregulation of protein expression leads to cardiac hypertrophy. MuRF1 gene point mutations have been found to generate protein aggregate myopathies (PAMs) defined as muscle disorder characterized by protein accumulation in muscle fibers. We have discovered that MuRF1 turned out to be also a target for a new post-translational modification arbitrated by conjugation of SUMO-1 and it is mediated by the SUMO ligases E2 UBC9 and the E3 PIASγ/4...
June 4, 2018: Journal of Molecular Cell Biology
Xing Guo, Yan-Qing Li, Ming-Shan Wang, Zhi-Bin Wang, Quan Zhang, Yong Shao, Run-Shen Jiang, Sheng Wang, Chen-Dong Ma, Robert W Murphy, Guang-Qin Wang, Jing Dong, Li Zhang, Dong-Dong Wu, Bing-Wang Du, Min-Sheng Peng, Ya-Ping Zhang
No abstract text is available yet for this article.
June 4, 2018: Journal of Molecular Cell Biology
Qi Yang, Jielin Tang, Rongjuan Pei, XiaoXiao Gao, Jing Guo, Chonghui Xu, Yun Wang, Qian Wang, Chunchen Wu, Yuan Zhou, Xue Hu, He Zhao, Yanyi Wang, Xinwen Chen, Jizheng Chen
Class II HDACs, such as HDAC4, are critical regulators of the immune response in various immune cells; however, its role in innate immunity remains largely unknown. Here, we report that the overexpression of HDAC4 suppresses the production of type I interferons triggered by pattern-recognition receptors (PRRs). HDAC4 repressed the translocation of transcription factor IRF3 to the nucleus, thereby decreasing IRF3-mediated IFN-β expression. In particular, we also determined that HDAC4 can be phosphorylated and simultaneously block the phosphorylation of IRF3 at Ser386 and Ser396 by TBK1 and IKKε, respectively, by interacting with the kinase domain of TBK1 and IKKε...
May 25, 2018: Journal of Molecular Cell Biology
Jiarui Wu
No abstract text is available yet for this article.
June 1, 2018: Journal of Molecular Cell Biology
Daebeom Park, Ho-Sung Lee, Jun Hyuk Kang, Seon-Myeong Kim, Jeong-Ryeol Gong, Kwang-Hyun Cho
Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure (HF), a global leading cause of death, and are regulated through the complicated intracellular signaling network, limiting the development of effective treatments due to its complexity. To identify effective therapeutic strategies for HF at a system level, we develop a large-scale comprehensive mathematical model of the cardiac signaling network by integrating all available experimental evidence. Attractor landscape analysis of the network model identifies distinct sets of control nodes that effectively suppress apoptosis and hypertrophy of cardiomyocytes under ischemic or pressure overload-induced HF, the two major types of HF...
June 1, 2018: Journal of Molecular Cell Biology
Xueyan Ma, Peixue Li, Peihao Chen, Jinhui Li, Hongling Huang, Chao Wang, Wenjing Li, Jianping Ding, Yun Zhao, Fa-Xing Yu, Xiangbing Qi, Lei Zhang
No abstract text is available yet for this article.
June 1, 2018: Journal of Molecular Cell Biology
Xianfa Yang, Ran Wang, Xiongjun Wang, Guoqing Cai, Yun Qian, Su Feng, Fangzhi Tan, Kun Chen, Ke Tang, Xingxu Huang, Naihe Jing, Yunbo Qiao
Clinical therapies of pluripotent stem cells (PSCs)-based transplantation have been hindered by frequent development of teratomas or tumors in animal models and clinical patients. Therefore, clarifying the mechanism of carcinogenesis in stem cell therapy is of great importance for reducing the risk of tumorigenicity. Here we differentiate Oct4-GFP mouse embryonic stem cells (mESCs) into neural progenitor cells (NPCs) and find that a minority of Oct4+ cells are continuously sustained at Oct4+ state. These cells can be enriched and proliferated in a standard ESC medium...
June 1, 2018: 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...
June 1, 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 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...
June 1, 2018: 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 the 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...
June 1, 2018: Journal of Molecular Cell Biology
Zizhang Zhou, Xia Yao, Shu Pang, Ping Chen, Weirong Jiang, Zhaoliang Shan, Qing Zhang
The Hedgehog (Hh) signaling pathway plays important roles in developmental processes including pattern formation and tissue homeostasis. The seven-pass transmembrane receptor Smoothened (Smo) is the pivotal transducer in the pathway; it, and thus the pathway overall, is regulated by ubiquitin-mediated degradation, which occurs in the absence of Hh. In the presence of Hh, the ubiquitination levels of Smo are decreased, but the molecular basis for this outcome is not well understood. Here, we identify the deubiquitinase UCHL5 as a positive regulator of the Hh pathway...
June 1, 2018: Journal of Molecular Cell Biology
Christopher N J Young, Natalia Chira, Justyna Róg, Rasha Al-Khalidi, Magalie Benard, Ludovic Galas, Philippe Chan, David Vaudry, Krzysztof Zablocki, Dariusz C Górecki
P2X7 purinoceptor promotes survival or cytotoxicity depending on extracellular adenosine triphosphate (ATP) stimulus intensity controlling its ion channel or P2X7-dependent large pore (LP) functions. Mechanisms governing this operational divergence and functional idiosyncrasy are ill-understood. We have discovered a feedback loop where sustained activation of P2X7 triggers release of active matrix metalloproteinase 2 (MMP-2), which halts ion channel and LP responses via the MMP-2-dependent receptor cleavage...
June 1, 2018: Journal of Molecular Cell Biology
Zhixiong Dong, Changjun Zhu, Qimin Zhan, Wei Jiang
The chromokinesin Kif4A controls proper chromosome condensation, congression/alignment, and cytokinesis to ensure faithful genetic inheritance. Here, we report that Cdk phosphorylation of human Kif4A at T1161 licenses Kif4A chromosomal localization, which, in turn, controls Kif4A early mitotic function. Phosphorylated Kif4A (Kif4AWT) or Cdk phospho-mimetic Kif4A mutant (Kif4ATE) associated with chromosomes and condensin I (non-SMC subunit CAP-G and core subunit SMC2) to regulate chromosome condensation, spindle morphology, and chromosome congression/alignment in early mitosis...
May 16, 2018: Journal of Molecular Cell Biology
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