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  • Long non-coding RNA NEAT1-centric gene regulation
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-26
    Ziqiang Wang, Kun Li, Weiren Huang

    Abstract Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA that is widely expressed in a variety of mammalian cell types. An increasing number of studies have demonstrated that NEAT1 plays key roles in various biological and pathological processes; therefore, it is important to understand how its expression is regulated and how it regulates the expression of its target genes

  • Controversies in TWEAK-Fn14 signaling in skeletal muscle atrophy and regeneration
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-21
    Amy L. Pascoe, Amelia J. Johnston, Robyn M. Murphy

    Abstract Skeletal muscle is one of the largest functional tissues in the human body; it is highly plastic and responds dramatically to anabolic and catabolic stimuli, including weight training and malnutrition, respectively. Excessive loss of muscle mass, or atrophy, is a common symptom of many disease states with severe impacts on prognosis and quality of life. TNF-like weak inducer of apoptosis (TWEAK)

  • Xist attenuates acute inflammatory response by female cells
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-19
    Botros B. Shenoda, Sujay Ramanathan, Richa Gupta, Yuzhen Tian, Renee Jean-Toussaint, Guillermo M. Alexander, Sankar Addya, Srinivas Somarowthu, Ahmet Sacan, Seena K. Ajit

    Abstract Biological sex influences inflammatory response, as there is a greater incidence of acute inflammation in men and chronic inflammation in women. Here, we report that acute inflammation is attenuated by X-inactive specific transcript (Xist), a female cell-specific nuclear long noncoding RNA crucial for X-chromosome inactivation. Lipopolysaccharide-mediated acute inflammation increased Xist

  • Plant vascular development: mechanisms and environmental regulation
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-19
    Javier Agustí, Miguel A. Blázquez

    Abstract Plant vascular development is a complex process culminating in the generation of xylem and phloem, the plant transporting conduits. Xylem and phloem arise from specialized stem cells collectively termed (pro)cambium. Once developed, xylem transports mainly water and mineral nutrients and phloem transports photoassimilates and signaling molecules. In the past few years, major advances have

  • Biological roles of LSD1 beyond its demethylase activity
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-19
    Feiying Gu, Yuxin Lin, Zhun Wang, Xiaoxin Wu, Zhenyue Ye, Yuezhen Wang, Huiyin Lan

    Abstract It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions

  • The Map3k12 (Dlk)/JNK3 signaling pathway is required for pancreatic beta-cell proliferation during postnatal development
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-18
    Mathie Tenenbaum, Valérie Plaisance, Raphael Boutry, Valérie Pawlowski, Cécile Jacovetti, Clara Sanchez-Parra, Hélène Ezanno, Julien Bourry, Nicole Beeler, Gianni Pasquetti, Valery Gmyr, Stéphane Dalle, Julie Kerr-Conte, François Pattou, Syu-ichi Hirai, Romano Regazzi, Amélie Bonnefond, Philippe Froguel, Amar Abderrahmani

    Abstract Unveiling the key pathways underlying postnatal beta-cell proliferation can be instrumental to decipher the mechanisms of beta-cell mass plasticity to increased physiological demand of insulin during weight gain and pregnancy. Using transcriptome and global Serine Threonine Kinase activity (STK) analyses of islets from newborn (10 days old) and adult rats, we found that highly proliferative

  • Building sophisticated sensors of extracellular cues that enable mammalian cells to work as “doctors” in the body
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-17
    Ryosuke Kojima, Dominque Aubel, Martin Fussenegger

    Abstract Mammalian cells are inherently capable of sensing extracellular environmental signals and activating complex biological functions on demand. Advances in synthetic biology have made it possible to install additional capabilities, which can allow cells to sense the presence of custom biological molecules and provide defined outputs on demand. When implanted/infused in patients, such engineered

  • Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-14
    Indiwari Gopallawa, Jenna R. Freund, Robert J. Lee

    Abstract Bitter taste receptors (T2Rs) are GPCRs involved in detection of bitter compounds by type 2 taste cells of the tongue, but are also expressed in other tissues throughout the body, including the airways, gastrointestinal tract, and brain. These T2Rs can be activated by several bacterial products and regulate innate immune responses in several cell types. Expression of T2Rs has been demonstrated

  • Molecular and circuit mechanisms regulating cocaine memory
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-14
    Brooke N. Bender, Mary M. Torregrossa

    Abstract Risk of relapse is a major challenge in the treatment of substance use disorders. Several types of learning and memory mechanisms are involved in substance use and have implications for relapse. Associative memories form between the effects of drugs and the surrounding environmental stimuli, and exposure to these stimuli during abstinence causes stress and triggers drug craving, which can

  • Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-13
    Jiacheng Deng, Zhichao Ni, Wenduo Gu, Qishan Chen, Witold Norbert Nowak, Ting Chen, Shirin Issa Bhaloo, Zhongyi Zhang, Yanhua Hu, Bin Zhou, Li Zhang, Qingbo Xu

    Abstract Stem/progenitor cells (SPCs) have been implicated to participate in vascular repair. However, the exact role of SPCs in endothelial repair of large vessels still remains controversial. This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing (scRNA-seq) and genetic lineage tracing mouse

  • Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-13
    Jianling Xie, Kaikai Shen, Ashley T. Jones, Jian Yang, Andrew R. Tee, Ming Hong Shen, Mengyuan Yu, Swati Irani, Derick Wong, James E. Merrett, Roman V. Lenchine, Stuart De Poi, Kirk B. Jensen, Paul J. Trim, Marten F. Snel, Makoto Kamei, Sally Kim Martin, Stephen Fitter, Shuye Tian, Xuemin Wang, Lisa M. Butler, Andrew C. W. Zannettino, Christopher G. Proud

    Abstract eIF4E plays key roles in protein synthesis and tumorigenesis. It is phosphorylated by the kinases MNK1 and MNK2. Binding of MNKs to eIF4G enhances their ability to phosphorylate eIF4E. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G. These effects provide

  • Update on SLC6A14 in lung and gastrointestinal physiology and physiopathology: focus on cystic fibrosis
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-12
    Manon Ruffin, Julia Mercier, Claire Calmel, Julie Mésinèle, Jeanne Bigot, Erika N. Sutanto, Anthony Kicic, Harriet Corvol, Loic Guillot

    Abstract The solute carrier family 6 member 14 (SLC6A14) protein imports and concentrates all neutral amino acids as well as the two cationic acids lysine and arginine into the cytoplasm of different cell types. Primarily described as involved in several cancer and colonic diseases physiopathological mechanisms, the SLC6A14 gene has been more recently identified as a genetic modifier of cystic fibrosis

  • Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-11
    Tiziana Caputo, Van Du T. Tran, Nasim Bararpour, Carine Winkler, Gabriela Aguileta, Khanh Bao Trang, Greta M. P. Giordano Attianese, Anne Wilson, Aurelien Thomas, Marco Pagni, Nicolas Guex, Béatrice Desvergne, Federica Gilardi

    Abstract Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet

  • Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-05
    Dong-Gyun Kim, Sujin Cho, Kyu-Yeon Lee, Seung-Ho Cheon, Hye-Jin Yoon, Joo-Youn Lee, Dongyoon Kim, Kwang-Soo Shin, Choong-Hyun Koh, Ji Sung Koo, Yuri Choi, Hyung Ho Lee, Yu-Kyoung Oh, Yoo-Seong Jeong, Suk-Jae Chung, Moonkyu Baek, Kwan-Young Jung, Hyo Jin Lim, Hyoun Sook Kim, Sung Jean Park, Jeong-Yeon Lee, Sang Jae Lee, Bong-Jin Lee

    Abstract NAD(P)-dependent steroid dehydrogenase-like (NSDHL), an essential enzyme in human cholesterol synthesis and a regulator of epidermal growth factor receptor (EGFR) trafficking pathways, has attracted interest as a therapeutic target due to its crucial relevance to cholesterol-related diseases and carcinomas. However, the development of pharmacological agents for targeting NSDHL has been hindered

  • The SF3b complex: splicing and beyond
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-05
    Chengfu Sun

    Abstract The SF3b complex is an intrinsic component of the functional U2 small nuclear ribonucleoprotein (snRNP). As U2 snRNP enters nuclear pre-mRNA splicing, SF3b plays key roles in recognizing the branch point sequence (BPS) and facilitating spliceosome assembly and activation. Since the discovery of SF3b, substantial progress has been made in elucidating its molecular mechanism during splicing

  • Regulation of B-cell function by NF-kappaB c-Rel in health and disease
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-04
    Shrikanth C. Basavarajappa, Parameswaran Ramakrishnan

    Abstract B cells mediate humoral immune response and contribute to the regulation of cellular immune response. Members of the Nuclear Factor kappaB (NF-κB) family of transcription factors play a major role in regulating B-cell functions. NF-κB subunit c-Rel is predominantly expressed in lymphocytes, and in B cells, it is required for survival, proliferation, and antibody production. Dysregulation of

  • Molecular characterization of an aquaporin-2 mutation causing a severe form of nephrogenic diabetes insipidus
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2019-07-13
    Emel Saglar Ozer, Hanne B. Moeller, Tugce Karaduman, Robert A. Fenton, Hatice Mergen

    Abstract The water channel aquaporin 2 (AQP2) is responsible for water reabsorption by kidney collecting duct cells. A substitution of amino acid leucine 137 to proline in AQP2 (AQP2-L137P) causes Nephrogenic Diabetes Insipidus (NDI). This study aimed to determine the cell biological consequences of this mutation on AQP2 function. Studies were performed in HEK293 and MDCK type I cells, transfected

  • Src and Fyn define a new signaling cascade activated by canonical and non-canonical Wnt ligands and required for gene transcription and cell invasion
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2019-07-16
    Aida Villarroel, Beatriz del Valle-Pérez, Guillem Fuertes, Josué Curto, Neus Ontiveros, Antonio Garcia de Herreros, Mireia Duñach

    Abstract Wnt ligands signal through canonical or non-canonical signaling pathways. Although both routes share common elements, such as the Fz2 receptor, they differ in the co-receptor and in many of the final responses; for instance, whereas canonical Wnts increase β-catenin stability, non-canonical ligands downregulate it. However, both types of ligands stimulate tumor cell invasion. We show here

  • miR-221 and -222 target CACNA1C and KCNJ5 leading to altered cardiac ion channel expression and current density
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2019-07-16
    Stephanie Binas, Maria Knyrim, Julia Hupfeld, Udo Kloeckner, Sindy Rabe, Sigrid Mildenberger, Katja Quarch, Nicole Strätz, Danny Misiak, Michael Gekle, Claudia Grossmann, Barbara Schreier

    Abstract MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among others cardiac hypertrophy and atrial fibrillation. The aim of our study was to evaluate the impact of miR-221/222 on cardiac electrical remodeling. Cardiac miR expression was analyzed in a mouse model with altered electrocardiography parameters and severe heart hypertrophy. Next generation sequencing revealed

  • Purinergic P2Y 2 receptors modulate endothelial sprouting
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2019-07-05
    Severin Mühleder, Christiane Fuchs, José Basílio, Dorota Szwarc, Karoline Pill, Krystyna Labuda, Paul Slezak, Christian Siehs, Johannes Pröll, Eleni Priglinger, Carsten Hoffmann, Wolfgang G. Junger, Heinz Redl, Wolfgang Holnthoner

    Abstract Purinergic P2 receptors are critical regulators of several functions within the vascular system, including platelet aggregation, vascular inflammation, and vascular tone. However, a role for ATP release and P2Y receptor signalling in angiogenesis remains poorly defined. Here, we demonstrate that blood vessel growth is controlled by P2Y2 receptors. Endothelial sprouting and vascular tube formation

  • Knockout of beta-2 microglobulin enhances cardiac repair by modulating exosome imprinting and inhibiting stem cell-induced immune rejection
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2019-07-16
    Lianbo Shao, Yu Zhang, Xiangbin Pan, Bin Liu, Chun Liang, Yuqing Zhang, Yanli Wang, Bing Yan, Wenping Xie, Yi Sun, Zhenya Shen, Xi-Yong Yu, Yangxin Li

    Abstract Background and aims Allogeneic human umbilical mesenchymal stem cells (alloUMSC) are convenient cell source for stem cell-based therapy. However, immune rejection is a major obstacle for clinical application of alloUMSC for cardiac repair after myocardial infarction (MI). The immune rejection is due to the presence of human leukocyte antigen (HLA) class I molecule which is increased during

  • Isotope metallomics approaches for medical research
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-04
    Brandon Mahan, Roger S. Chung, Dean L. Pountney, Frédéric Moynier, Simon Turner

    Abstract Metallomics is a rapidly evolving field of bio-metal research that integrates techniques and perspectives from other “-omics” sciences (e.g. genomics, proteomics) and from research vocations further afield. Perhaps the most esoteric of this latter category has been the recent coupling of biomedicine with element and isotope geochemistry, commonly referred to as isotope metallomics. Over the

  • Apelin/APJ system: an emerging therapeutic target for respiratory diseases.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-03
    Jialong Yan,Aiping Wang,Jiangang Cao,Linxi Chen

    Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary

  • Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-03-02
    Martina G L Perego,Noemi Galli,Monica Nizzardo,Alessandra Govoni,Michela Taiana,Nereo Bresolin,Giacomo P Comi,Stefania Corti

    Spinal muscular atrophy (SMA) with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease that is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory distress. Without intervention, infants with the severe form of the disease die before 2 years of age. SMARD1 is caused by mutations in the IGHMBP2 gene that determine a deficiency

  • Cellular uptake of collagens and implications for immune cell regulation in disease.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-25
    Henrik J Jürgensen,Sander van Putten,Kirstine S Nørregaard,Thomas H Bugge,Lars H Engelholm,Niels Behrendt,Daniel H Madsen

    As the dominant constituent of the extracellular matrix (ECM), collagens of different types are critical for the structural properties of tissues and make up scaffolds for cellular adhesion and migration. Importantly, collagens also directly modulate the phenotypic state of cells by transmitting signals that influence proliferation, differentiation, polarization, survival, and more, to cells of mesenchymal

  • The neglected part of early embryonic development: maternal protein degradation
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-24
    Tereza Toralova, Veronika Kinterova, Eva Chmelikova, Jiri Kanka

    Abstract The degradation of maternally provided molecules is a very important process during early embryogenesis. However, the vast majority of studies deals with mRNA degradation and protein degradation is only a very little explored process yet. The aim of this article was to summarize current knowledge about the protein degradation during embryogenesis of mammals. In addition to resuming of known

  • Regulation of branched-chain amino acid metabolism by hypoxia-inducible factor in glioblastoma.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-22
    Bo Zhang,Yan Chen,Xiaolei Shi,Mi Zhou,Lei Bao,Kimmo J Hatanpaa,Toral Patel,Ralph J DeBerardinis,Yingfei Wang,Weibo Luo

    Hypoxia-inducible factors (HIFs) mediate metabolic reprogramming in response to hypoxia. However, the role of HIFs in branched-chain amino acid (BCAA) metabolism remains unknown. Here we show that hypoxia upregulates mRNA and protein levels of the BCAA transporter LAT1 and the BCAA metabolic enzyme BCAT1, but not their paralogs LAT2-4 and BCAT2, in human glioblastoma (GBM) cell lines as well as primary

  • Functional mosaic organization of neuroligins in neuronal circuits.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-20
    Liming Qin,Sile Guo,Ying Han,Xiankun Wang,Bo Zhang

    Complex brain circuitry with feedforward and feedback systems regulates neuronal activity, enabling neural networks to process and drive the entire spectrum of cognitive, behavioral, sensory, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits is underpinned by hundreds of synaptic adhesion molecules that span synaptic junctions. Dysfunction of a single

  • Revisiting cellular immune response to oncogenic Marek's disease virus: the rising of avian T-cell immunity.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-20
    Yi Yang,Maoli Dong,Xiaoli Hao,Aijian Qin,Shaobin Shang

    Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. Although Marek's disease (MD) is well controlled by current vaccines, the evolution of MDV field viruses towards increasing virulence is concerning as a better vaccine to combat very virulent plus MDV is still lacking. Our understanding

  • Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-19
    T E Thingholm,L Rönnstrand,P A Rosenberg

    Zinc is required for the regulation of proliferation, metabolism, and cell signaling. It is an intracellular second messenger, and the cellular level of ionic, mobile zinc is strictly controlled by zinc transporters. In mammals, zinc homeostasis is primarily regulated by ZIP and ZnT zinc transporters. The importance of these transporters is underscored by the list of diseases resulting from changes

  • Reductive stress in striated muscle cells.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-18
    Ilaria Bellezza,Francesca Riuzzi,Sara Chiappalupi,Cataldo Arcuri,Ileana Giambanco,Guglielmo Sorci,Rosario Donato

    Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/NAD+ ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor

  • Targets for protection and mitigation of radiation injury.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-18
    Ehsan Khodamoradi,Mojtaba Hoseini-Ghahfarokhi,Peyman Amini,Elahe Motevaseli,Dheyauldeen Shabeeb,Ahmed Eleojo Musa,Masoud Najafi,Bagher Farhood

    Protection of normal tissues against toxic effects of ionizing radiation is a critical issue in clinical and environmental radiobiology. Investigations in recent decades have suggested potential targets that are involved in the protection against radiation-induced damages to normal tissues and can be proposed for mitigation of radiation injury. Emerging evidences have been shown to be in contrast to

  • The Rab5 activator RME-6 is required for amyloid precursor protein endocytosis depending on the YTSI motif.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-17
    Simone Eggert,Tomas Gruebl,Ritu Rajender,Carsten Rupp,Bianca Sander,Amelie Heesch,Marius Zimmermann,Sebastian Hoepfner,Hanswalter Zentgraf,Stefan Kins

    Endocytosis of the amyloid precursor protein (APP) is critical for generation of β-amyloid, aggregating in Alzheimer's disease. APP endocytosis depending on the intracellular NPTY motif is well investigated, whereas involvement of the YTSI (also termed BaSS) motif remains controversial. Here, we show that APP lacking the YTSI motif (ΔYTSI) displays reduced localization to early endosomes and decreased

  • Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-15
    Dong Wang,Redouane Tabti,Sabria Elderwish,Hussein Abou-Hamdan,Amel Djehal,Peng Yu,Hajime Yurugi,Krishnaraj Rajalingam,Canan G Nebigil,Laurent Désaubry

    Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of signaling pathways in health and diseases. Small molecules targeting PHBs display promising effects against cancers, osteoporosis, inflammatory, cardiac and neurodegenerative diseases. This review provides an updated overview of the various classes of PHB ligands

  • Founder cells for hepatocytes during liver regeneration: from identification to application.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-14
    Saisai Wei,Jiacheng Tang,Xiujun Cai

    Liver regeneration (LR) capacity in vertebrates developed through natural selection over a hundred million years of evolution. To maintain homeostasis or recover from various injuries, liver cells must regenerate; this process includes the renewal of parenchymal and nonparenchymal cells as well as the formation of liver structures. The cellular origin of newly grown tissue is one of the critical questions

  • Physiological functions of SPP/SPPL intramembrane proteases.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-12
    Torben Mentrup,Florencia Cabrera-Cabrera,Regina Fluhrer,Bernd Schröder

    Intramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism

  • Prevalence and significance of the commonest phosphorylated motifs in the human proteome: a global analysis.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-12
    Luca Cesaro,Lorenzo A Pinna

    Protein phosphorylation is the most frequent post-translational modification by which the properties of eukaryotic proteins can be reversibly modified. In humans, over 500 protein kinases generate a huge phosphoproteome including more than 200,000 individual phosphosites, a figure which is still continuously increasing. The in vivo selectivity of protein kinases is the outcome of a multifaceted and

  • Dynamics of kinetochore structure and its regulations during mitotic progression.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-12
    Masatoshi Hara,Tatsuo Fukagawa

    Faithful chromosome segregation during mitosis in eukaryotes requires attachment of the kinetochore, a large protein complex assembled on the centromere of each chromosome, to the spindle microtubules. The kinetochore is a structural interface for the microtubule attachment and provides molecular surveillance mechanisms that monitor and ensure the precise microtubule attachment as well, including error

  • Abnormal X chromosome inactivation and tumor development.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-10
    Dan Wang,Le Tang,Yingfen Wu,Chunmei Fan,Shanshan Zhang,Bo Xiang,Ming Zhou,Xiaoling Li,Yong Li,Guiyuan Li,Wei Xiong,Zhaoyang Zeng,Can Guo

    During embryonic development, one of the two X chromosomes of a mammalian female cell is randomly inactivated by the X chromosome inactivation mechanism, which is mainly dependent on the regulation of the non-coding RNA X-inactive specific transcript at the X chromosome inactivation center. There are three proteins that are essential for X-inactive specific transcript to function properly: scaffold

  • Beta-arrestins operate an on/off control switch for focal adhesion kinase activity.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-10
    Revu Ann Alexander,Isaure Lot,Kusumika Saha,Guillaume Abadie,Mireille Lambert,Eleonore Decosta,Hiroyuki Kobayashi,Alexandre Beautrait,Aurélie Borrull,Atef Asnacios,Michel Bouvier,Mark G H Scott,Stefano Marullo,Hervé Enslen

    Focal adhesion kinase (FAK) regulates key biological processes downstream of G protein-coupled receptors (GPCRs) in normal and cancer cells, but the modes of kinase activation by these receptors remain unclear. We report that after GPCR stimulation, FAK activation is controlled by a sequence of events depending on the scaffolding proteins β-arrestins and G proteins. Depletion of β-arrestins results

  • Synaptic mitochondrial dysfunction and septin accumulation are linked to complement-mediated synapse loss in an Alzheimer's disease animal model.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-07
    Balázs A Györffy,Vilmos Tóth,György Török,Péter Gulyássy,Réka Á Kovács,Henrietta Vadászi,András Micsonai,Melinda E Tóth,Miklós Sántha,László Homolya,László Drahos,Gábor Juhász,Katalin A Kékesi,József Kardos

    Synaptic functional disturbances with concomitant synapse loss represent central pathological hallmarks of Alzheimer's disease. Excessive accumulation of cytotoxic amyloid oligomers is widely recognized as a key event that underlies neurodegeneration. Certain complement components are crucial instruments of widespread synapse loss because they can tag synapses with functional impairments leading to

  • A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-06
    Sihyeon An,Oh Sung Kwon,Jinbae Yu,Sung Key Jang

    During mitosis, translation of most mRNAs is strongly repressed; none of the several explanatory hypotheses suggested can fully explain the molecular basis of this phenomenon. Here we report that cyclin-dependent CDK11/p58-a serine/threonine kinase abundantly expressed during M phase-represses overall translation by phosphorylating a subunit (eIF3F) of the translation factor eIF3 complex that is essential

  • Misfolded amyloid-β-42 impairs the endosomal-lysosomal pathway.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-05
    Karen E Marshall,Devkee M Vadukul,Kevin Staras,Louise C Serpell

    Misfolding and aggregation of proteins is strongly linked to several neurodegenerative diseases, but how such species bring about their cytotoxic actions remains poorly understood. Here we used specifically-designed optical reporter probes and live fluorescence imaging in primary hippocampal neurons to characterise the mechanism by which prefibrillar, oligomeric forms of the Alzheimer's-associated

  • CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-04
    Na Li,Panpan Jiang,Anwei Chen,Xi Luo,Yukai Jing,Lu Yang,Danqing Kang,Qiuyue Chen,Ju Liu,Jiang Chang,Julia Jellusova,Heather Miller,Lisa Westerberg,Cong-Yi Wang,Quan Gong,Chaohong Liu

    As an important chemokine receptor, the role of CX3CR1 has been studied extensively on the migration of lymphocytes including T and B cells. Although CX3CR1+ B cells have immune suppressor properties, little is known about its role on the regulation of BCR signaling and B cell differentiation as well as the underlying molecular mechanism. We have used CX3CR1 KO mice to study the effect of CX3CR1 deficiency

  • Functional and transcriptomic analyses of the NF-Y family provide insights into the defense mechanisms of honeybees under adverse circumstances.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-03
    Guilin Li,Hang Zhao,Hongbin Guo,Ying Wang,Xuepei Cui,Baohua Xu,Xingqi Guo

    As predominant pollinators, honeybees are important for crop production and terrestrial ecosystems. Recently, various environmental stresses have led to large declines in honeybee populations in many regions. The ability of honeybees to respond to these stresses is critical for their survival. However, the details of the stress defense mechanisms of honeybees have remained elusive. Here, we found that

  • Endosymbiosis before eukaryotes: mitochondrial establishment in protoeukaryotes.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-01
    István Zachar,Gergely Boza

    Endosymbiosis and organellogenesis are virtually unknown among prokaryotes. The single presumed example is the endosymbiogenetic origin of mitochondria, which is hidden behind the event horizon of the last eukaryotic common ancestor. While eukaryotes are monophyletic, it is unlikely that during billions of years, there were no other prokaryote-prokaryote endosymbioses as symbiosis is extremely common

  • Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-01
    Chao-Tao Tang,Qing-Wei Zhang,Shan Wu,Ming-Yu Tang,Qian Liang,Xiao-Lu Lin,Yun-Jie Gao,Zhi-Zheng Ge

    BACKGROUND Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. METHODS We took advantage

  • EMT signaling: potential contribution of CRISPR/Cas gene editing.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-01
    Reza Mohammadinejad,Alessio Biagioni,Ganesan Arunkumar,Rebecca Shapiro,Kun-Che Chang,Mohammed Sedeeq,Aftab Taiyab,Mohammad Hashemabadi,Abbas Pardakhty,Ali Mandegary,Jean-Paul Thiery,Amir Reza Aref,Iman Azimi

    Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced

  • Epigenetic regulation of centromere function.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-02-01
    Charmaine Yan Yu Wong,Bernard Chi Hang Lee,Karen Wing Yee Yuen

    The centromere is a specialized region on the chromosome that directs equal chromosome segregation. Centromeres are usually not defined by DNA sequences alone. How centromere formation and function are determined by epigenetics is still not fully understood. Active centromeres are often marked by the presence of centromeric-specific histone H3 variant, centromere protein A (CENP-A). How CENP-A is assembled

  • Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-31
    Sevda Jafari,Ommoleila Molavi,Houman Kahroba,Mohammad Saied Hejazi,Nasrin Maleki-Dizaji,Siamak Barghi,Seyed Hossein Kiaie,Farhad Jadidi-Niaragh

    Immunotherapy is considered as an effective method for cancer treatment owing to the induction of specific and long-lasting anti-cancer effects. Immunotherapeutic strategies have shown significant success in human malignancies, particularly in prostate cancer (PCa), a major global health issue regarding its high metastatic rates. In fact, the first cancer vaccine approved by FDA was Provenge, which

  • The neuroscience of sugars in taste, gut-reward, feeding circuits, and obesity.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-31
    Ranier Gutierrez,Esmeralda Fonseca,Sidney A Simon

    Throughout the animal kingdom sucrose is one of the most palatable and preferred tastants. From an evolutionary perspective, this is not surprising as it is a primary source of energy. However, its overconsumption can result in obesity and an associated cornucopia of maladies, including type 2 diabetes and cardiovascular disease. Here we describe three physiological levels of processing sucrose that

  • Infection and atherosclerosis: TLR-dependent pathways.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-30
    Bowei Li,Yuanpeng Xia,Bo Hu

    Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is

  • Adenosine-to-inosine RNA editing in the immune system: friend or foe?
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-29
    Taisuke Nakahama,Yukio Kawahara

    Our body expresses sensors to detect pathogens through the recognition of expressed molecules, including nucleic acids, lipids, and proteins, while immune tolerance prevents an overreaction with self and the development of autoimmune disease. Adenosine (A)-to-inosine (I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a post-transcriptional modification that can potentially

  • Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-25
    Jacques Vanderstraeten,Philippe Gailly,E Pascal Malkemper

    The mechanisms that synchronize the biorhythms of the mammalian retina with the light/dark cycle are independent of those synchronizing the rhythms in the central pacemaker, the suprachiasmatic nucleus. The identity of the photoreceptor(s) responsible for the light entrainment of the retina of mammals is still a matter of debate, and recent studies have reported contradictory results in this respect

  • The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-23
    Michele Sommariva,Valentino Le Noci,Francesca Bianchi,Simone Camelliti,Andrea Balsari,Elda Tagliabue,Lucia Sfondrini

    Like other body districts, lungs present a complex bacteria community. An emerging function of lung microbiota is to promote and maintain a state of immune tolerance, to prevent uncontrolled and not desirable inflammatory response caused by inhalation of harmless environmental stimuli. This effect is mediated by a continuous dialog between commensal bacteria and immune cells resident in lungs, which

  • A SYK/SHC1 pathway regulates the amount of CFTR in the plasma membrane.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-23
    Cláudia Almeida Loureiro,Francisco R Pinto,Patrícia Barros,Paulo Matos,Peter Jordan

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the recessive genetic disease cystic fibrosis, where the chloride transport across the apical membrane of epithelial cells mediated by the CFTR protein is impaired. CFTR protein trafficking to the plasma membrane (PM) is the result of a complex interplay between the secretory and membrane recycling pathways that

  • The mechanisms of pathological extramedullary hematopoiesis in diseases.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-23
    Xinxin Yang,Degao Chen,Haixia Long,Bo Zhu

    Extramedullary hematopoiesis (EMH) is the expansion and differentiation of hematopoietic stem and progenitor cells outside of the bone marrow. In postnatal life, as a compensatory mechanism for ineffective hematopoiesis of the bone marrow, pathological EMH is triggered by hematopoietic disorders, insufficient hematopoietic compensation, and other pathological stress conditions, such as infection, advanced

  • Biomedical applications of electrical stimulation.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-23
    Siwei Zhao,Abijeet Singh Mehta,Min Zhao

    This review provides a comprehensive overview on the biomedical applications of electrical stimulation (EStim). EStim has a wide range of direct effects on both biomolecules and cells. These effects have been exploited to facilitate proliferation and functional development of engineered tissue constructs for regenerative medicine applications. They have also been tested or used in clinics for pain

  • The effect of fornix deep brain stimulation in brain diseases
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 

    Abstract Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson’s disease, epilepsy, and obsessive–compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain

  • Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis.
    Cell. Mol. Life Sci. (IF 7.014) Pub Date : 2020-01-22
    Russel J Reiter,Ramaswamy Sharma,Qiang Ma,Sergio Rorsales-Corral,Luiz G de Almeida Chuffa

    Melatonin has the ability to intervene in the initiation, progression and metastasis of some experimental cancers. A large variety of potential mechanisms have been advanced to describe the metabolic and molecular events associated with melatonin's interactions with cancer cells. There is one metabolic perturbation that is common to a large number of solid tumors and accounts for the ability of cancer

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全球疫情及响应:BMC Medicine专题征稿