The regulatory role of Myomaker and Myomixer-Myomerger-Minion in muscle development and regeneration.
Abstract Skeletal muscle plays essential roles in motor function, energy, and glucose metabolism. Skeletal muscle formation occurs through a process called myogenesis, in which a crucial step is the fusion of mononucleated myoblasts to form multinucleated myofibers. The myoblast/myocyte fusion is triggered and coordinated in a muscle-specific way that is essential for muscle development and post-natal muscle regeneration. Many molecules and proteins have been found and demonstrated to have the capacity to regulate the fusion of myoblast/myocytes. Interestingly, two newly discovered muscle-specific membrane protein...
Source: Cellular and Molecular Life Sciences : CMLS - October 22, 2019 Category: Cytology Authors: Chen B, You W, Wang Y, Shan T Tags: Cell Mol Life Sci Source Type: research

Homotrimeric MMP-9 is an active hitchhiker on alpha-2-macroglobulin partially escaping protease inhibition and internalization through LRP-1.
Abstract Proteolysis is a crucial process in life, tightly controlled by numerous natural protease inhibitors. In human blood, alpha-2-macroglobulin is an emergency protease inhibitor preventing coagulation and damage to endothelia and leukocytes. With the use of a unique protease trapping mechanism, alpha-2-macroglobulin lures active proteases into its snap-trap, shields these from potential substrates and 'flags' their complex for elimination by receptor-mediated endocytosis. Matrix metalloprotease-9/gelatinase B is a secreted protease increased in blood of patients with inflammations, vascular disorders and can...
Source: Cellular and Molecular Life Sciences : CMLS - October 22, 2019 Category: Cytology Authors: Serifova X, Ugarte-Berzal E, Opdenakker G, Vandooren J Tags: Cell Mol Life Sci Source Type: research

Inhibition of HIV replication through siRNA carried by CXCR4-targeted chimeric nanobody.
Abstract Small interfering RNA (siRNA) application in therapy still faces a major challenge with the lack of an efficient and specific delivery system. Current vehicles are often responsible for poor efficacy, safety concerns, and burden costs of siRNA-based therapeutics. Here, we describe a novel strategy for targeted delivery of siRNA molecules to inhibit human immunodeficiency virus (HIV) infection. Specific membrane translocation of siRNA inhibitor was addressed by an engineered nanobody targeting the HIV co-receptor CXCR4 (NbCXCR4) in fusion with a single-chain variable fragment (4M5.3) that carried the FITC-...
Source: Cellular and Molecular Life Sciences : CMLS - October 21, 2019 Category: Cytology Authors: Cunha-Santos C, Perdigao PRL, Martin F, Oliveira JG, Cardoso M, Manuel A, Taveira N, Goncalves J Tags: Cell Mol Life Sci Source Type: research

The role of E3 ubiquitin ligase HECTD3 in cancer and beyond.
Abstract Ubiquitin modification plays significant roles in protein fate determination, signaling transduction, and cellular processes. Over the past 2 decades, the number of studies on ubiquitination has demonstrated explosive growth. E3 ubiquitin ligases are the key enzymes that determine the substrate specificity and are involved in cancer. Several recent studies shed light on the functions and mechanisms of HECTD3 E3 ubiquitin ligase. This review describes the progress in the recent studies of HECTD3 in cancer and other diseases. We propose that HECTD3 is a potential biomarker and a therapeutic target, and disc...
Source: Cellular and Molecular Life Sciences : CMLS - October 20, 2019 Category: Cytology Authors: Jiang Q, Li F, Cheng Z, Kong Y, Chen C Tags: Cell Mol Life Sci Source Type: research

Nanoscale delivery systems for microRNAs in cancer therapy.
Abstract Concomitant with advances in research regarding the role of miRNAs in sustaining carcinogenesis, major concerns about their delivery options for anticancer therapies have been raised. The answer to this problem may come from the world of nanoparticles such as liposomes, exosomes, polymers, dendrimers, mesoporous silica nanoparticles, quantum dots and metal-based nanoparticles which have been proved as versatile and valuable vehicles for many biomolecules including miRNAs. In another train of thoughts, the general scheme of miRNA modulation consists in inhibition of oncomiRNA expression and restoration of ...
Source: Cellular and Molecular Life Sciences : CMLS - October 20, 2019 Category: Cytology Authors: Boca S, Gulei D, Zimta AA, Onaciu A, Magdo L, Tigu AB, Ionescu C, Irimie A, Buiga R, Berindan-Neagoe I Tags: Cell Mol Life Sci Source Type: research

Energy-converting hydrogenases: the link between H2 metabolism and energy conservation.
r V Abstract The reversible interconversion of molecular hydrogen and protons is one of the most ancient microbial metabolic reactions and catalyzed by hydrogenases. A widespread yet largely enigmatic group comprises multisubunit [NiFe] hydrogenases, that directly couple H2 metabolism to the electrochemical ion gradient across the membranes of bacteria and of archaea. These complexes are collectively referred to as energy-converting hydrogenases (Ech), as they reversibly transform redox energy into physicochemical energy. Redox energy is typically provided by a low potential electron donor such as reduced ferredox...
Source: Cellular and Molecular Life Sciences : CMLS - October 18, 2019 Category: Cytology Authors: Schoelmerich MC, Müller V Tags: Cell Mol Life Sci Source Type: research

The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis.
Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. Currently approved disease-modifying treatment modalities are immunomodulatory or immunosuppressive. While the applied drugs reduce the frequency and severity of the attacks, their efficacy to regenerate myelin membranes and to halt disease progression is limited. To achieve such therapeutic aims, understanding biological mechanisms of remyelination and identifying factors that interfere with remyelination in MS can give respective directions. Such a perspective is g...
Source: Cellular and Molecular Life Sciences : CMLS - October 17, 2019 Category: Cytology Authors: de Jong CGHM, Gabius HJ, Baron W Tags: Cell Mol Life Sci Source Type: research

Correction to: Adamts17 is  involved in skeletogenesis through modulation of BMP‑Smad1/5/8 pathway.
Correction to: Adamts17 is involved in skeletogenesis through modulation of BMP‑Smad1/5/8 pathway. Cell Mol Life Sci. 2019 Oct 16;: Authors: Oichi T, Taniguchi Y, Soma K, Oshima Y, Yano F, Mori Y, Chijimatsu R, Kim-Kaneyama JR, Tanaka S, Saito T Abstract In the published article, the Fig. 4a was published incorrectly. PMID: 31620828 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - October 15, 2019 Category: Cytology Authors: Oichi T, Taniguchi Y, Soma K, Oshima Y, Yano F, Mori Y, Chijimatsu R, Kim-Kaneyama JR, Tanaka S, Saito T Tags: Cell Mol Life Sci Source Type: research

Quorum sensing for population-level control of bacteria and potential therapeutic applications.
Abstract Quorum sensing (QS), a microbial cell-to-cell communication process, dynamically regulates a variety of metabolism and physiological activities. In this review, we provide an update on QS applications based on autoinducer molecules including acyl-homoserine lactones (AHLs), auto-inducing peptides (AIPs), autoinducer 2 (AI-2) and indole in population-level control of bacteria, and highlight the potential in developing novel clinical therapies. We summarize the development in the combination of various genetic circuits such as genetic oscillators, toggle switches and logic gates with AHL-based QS devices in...
Source: Cellular and Molecular Life Sciences : CMLS - October 13, 2019 Category: Cytology Authors: Wu S, Liu J, Liu C, Yang A, Qiao J Tags: Cell Mol Life Sci Source Type: research

Targeting DNA repair in cancer: current state and novel approaches.
Abstract DNA damage response, DNA repair and genomic instability have been under study for their role in tumor initiation and progression for many years now. More recently, next-generation sequencing on cancer tissue from various patient cohorts have revealed mutations and epigenetic silencing of various genes encoding proteins with roles in these processes. These findings, together with the unequivocal role of DNA repair in therapeutic response, have fueled efforts toward the clinical exploitation of research findings. The successful example of PARP1/2 inhibitors has also supported these efforts and led to numero...
Source: Cellular and Molecular Life Sciences : CMLS - October 13, 2019 Category: Cytology Authors: Klinakis A, Karagiannis D, Rampias T Tags: Cell Mol Life Sci Source Type: research

Phosphorylation-dependent regulation of the NOTCH1 intracellular domain by dual-specificity tyrosine-regulated kinase 2.
ega L, Calzado MA Abstract NOTCH proteins constitute a receptor family with a widely conserved role in cell cycle, growing and development regulation. NOTCH1, the best characterised member of this family, regulates the expression of key genes in cell growth and angiogenesis, playing an essential role in cancer development. These observations provide a relevant rationale to propose the inhibition of the intracellular domain of NOTCH1 (Notch1-IC) as a strategy for treating various types of cancer. Notch1-IC stability is mainly controlled by post-translational modifications. FBXW7 ubiquitin E3 ligase-mediated degrada...
Source: Cellular and Molecular Life Sciences : CMLS - October 10, 2019 Category: Cytology Authors: Morrugares R, Correa-Sáez A, Moreno R, Garrido-Rodríguez M, Muñoz E, de la Vega L, Calzado MA Tags: Cell Mol Life Sci Source Type: research

Qualitative analysis of contribution of intracellular skeletal changes to cellular elasticity.
Abstract Cells are dynamic structures that continually generate and sustain mechanical forces within their environments. Cells respond to mechanical forces by changing their shape, moving, and differentiating. These reactions are caused by intracellular skeletal changes, which induce changes in cellular mechanical properties such as stiffness, elasticity, viscoelasticity, and adhesiveness. Interdisciplinary research combining molecular biology with physics and mechanical engineering has been conducted to characterize cellular mechanical properties and understand the fundamental mechanisms of mechanotransduction. I...
Source: Cellular and Molecular Life Sciences : CMLS - October 10, 2019 Category: Cytology Authors: Kwon S, Kim KS Tags: Cell Mol Life Sci Source Type: research

Recent advances in the genetic basis of taste detection in Drosophila.
Abstract The insect gustatory system senses taste information from environmental food substrates and processes it to control feeding behaviors. Drosophila melanogaster has been a powerful genetic model for investigating how various chemical cues are detected at the molecular and cellular levels. In addition to an understanding of how tastants belonging to five historically described taste modalities (sweet, bitter, acid, salt, and amino acid) are sensed, recent findings have identified taste neurons and receptors that recognize tastants of non-canonical modalities, including fatty acids, carbonated water, polyamin...
Source: Cellular and Molecular Life Sciences : CMLS - October 8, 2019 Category: Cytology Authors: Chen YD, Dahanukar A Tags: Cell Mol Life Sci Source Type: research

ESCRT-III-associated proteins and spastin inhibit protrudin-dependent polarised membrane traffic.
Abstract Mutations in the gene encoding the microtubule severing ATPase spastin are the most frequent cause of hereditary spastic paraplegia, a genetic condition characterised by length-dependent axonal degeneration. Here, we show that HeLa cells lacking spastin and embryonic fibroblasts from a spastin knock-in mouse model become highly polarised and develop cellular protrusions. In HeLa cells, this phenotype was rescued by wild-type spastin, but not by forms unable to sever microtubules or interact with endosomal ESCRT-III proteins. Cells lacking the spastin-interacting ESCRT-III-associated proteins IST1 or CHMP1...
Source: Cellular and Molecular Life Sciences : CMLS - October 4, 2019 Category: Cytology Authors: Connell JW, Allison RJ, Rodger CE, Pearson G, Zlamalova E, Reid E Tags: Cell Mol Life Sci Source Type: research

Molecular basis of strigolactone perception in root-parasitic plants: aiming to control its germination with strigolactone agonists/antagonists.
Abstract The genus Striga, also called "witchweed", is a member of the family Orobanchaceae, which is a major family of root-parasitic plants. Striga can lead to the formation of seed stocks in the soil and to explosive expansion with enormous seed production and stability once the crops they parasitize are cultivated. Understanding the molecular mechanism underlying the communication between Striga and their host plants through natural seed germination stimulants, "strigolactones (SLs)", is required to develop the technology for Striga control. This review outlines recent findings on the SL pe...
Source: Cellular and Molecular Life Sciences : CMLS - October 4, 2019 Category: Cytology Authors: Miyakawa T, Xu Y, Tanokura M Tags: Cell Mol Life Sci Source Type: research

Molecular mechanisms underlying selective synapse formation of vertebrate retinal photoreceptor cells.
Abstract In vertebrate central nervous systems (CNSs), highly diverse neurons are selectively connected via synapses, which are essential for building an intricate neural network. The vertebrate retina is part of the CNS and is comprised of a distinct laminar organization, which serves as a good model system to study developmental synapse formation mechanisms. In the retina outer plexiform layer, rods and cones, two types of photoreceptor cells, elaborate selective synaptic contacts with ON- and/or OFF-bipolar cell terminals as well as with horizontal cell terminals. In the mouse retina, three photoreceptor subtyp...
Source: Cellular and Molecular Life Sciences : CMLS - October 3, 2019 Category: Cytology Authors: Furukawa T, Ueno A, Omori Y Tags: Cell Mol Life Sci Source Type: research

Time after time: circadian clock regulation of intestinal stem cells.
Abstract Daily fluctuations in animal physiology, known as circadian rhythms, are orchestrated by a conserved molecular timekeeper, known as the circadian clock. The circadian clock forms a transcription-translation feedback loop that has emerged as a central biological regulator of many 24-h processes. Early studies of the intestine discovered that many digestive functions have a daily rhythm and that intestinal cell production was similarly time-dependent. As genetic methods in model organisms have become available, it has become apparent that the circadian clock regulates many basic cellular functions, includin...
Source: Cellular and Molecular Life Sciences : CMLS - October 3, 2019 Category: Cytology Authors: Parasram K, Karpowicz P Tags: Cell Mol Life Sci Source Type: research

Distinct functions of TMC channels: a comparative overview.
Abstract In the past two decades, transmembrane channel-like (TMC) proteins have attracted a significant amount of research interest, because mutations of Tmc1 lead to hereditary deafness. As evolutionarily conserved membrane proteins, TMC proteins are widely involved in diverse sensorimotor functions of many species, such as hearing, chemosensation, egg laying, and food texture detection. Interestingly, recent structural and physiological studies suggest that TMC channels may share a similar membrane topology with the Ca2+-activated Cl- channel TMEM16 and the mechanically activated OSCA1.2/TMEM63 channel. Namely,...
Source: Cellular and Molecular Life Sciences : CMLS - October 3, 2019 Category: Cytology Authors: Yue X, Sheng Y, Kang L, Xiao R Tags: Cell Mol Life Sci Source Type: research

Caenorhabditis elegans: a model to understand host-microbe interactions.
Abstract Host-microbe interactions within the gut are fundamental to all higher organisms. Caenorhabditis elegans has been in use as a surrogate model to understand the conserved mechanisms in host-microbe interactions. Morphological and functional similarities of C. elegans gut with the human have allowed the mechanistic investigation of gut microbes and their effects on metabolism, development, reproduction, behavior, pathogenesis, immune responses and lifespan. Recent reports suggest their suitability for functional investigations of human gut bacteria, such as gut microbiota of healthy and diseased individuals...
Source: Cellular and Molecular Life Sciences : CMLS - October 3, 2019 Category: Cytology Authors: Kumar A, Baruah A, Tomioka M, Iino Y, Kalita MC, Khan M Tags: Cell Mol Life Sci Source Type: research

Light-induced modulation of the mitochondrial respiratory chain activity: possibilities and limitations.
Š, Dejneka A, Lunov O Abstract Biological effects of high fluence low-power (HFLP) lasers have been reported for some time, yet the molecular mechanisms procuring cellular responses remain obscure. A better understanding of the effects of HFLP lasers on living cells will be instrumental for the development of new experimental and therapeutic strategies. Therefore, we investigated sub-cellular mechanisms involved in the laser interaction with human hepatic cell lines. We show that mitochondria serve as sub-cellular "sensor" and "effector" of laser light non-specific interactions with cel...
Source: Cellular and Molecular Life Sciences : CMLS - October 2, 2019 Category: Cytology Authors: Lunova M, Smolková B, Uzhytchak M, Janoušková KŽ, Jirsa M, Egorova D, Kulikov A, Kubinová Š, Dejneka A, Lunov O Tags: Cell Mol Life Sci Source Type: research

Preterm neonatal immunology at the intestinal interface.
Abstract Fetal and neonatal development represents a critical window for setting a path toward health throughout life. In this review, we focus on intestinal immunity, how it develops, and its implications for subsequent neonatal diseases. We discuss maternal nutritional and environmental exposures that dictate outcomes for the developing fetus. Although still controversial, there is evidence in support of an in utero microbiome. Specific well-intentioned and routine applications of antibiotics, steroids, and surgical interventions implemented before, during, and after birth skew the neonate towards pro-inflammato...
Source: Cellular and Molecular Life Sciences : CMLS - September 30, 2019 Category: Cytology Authors: Van Belkum M, Mendoza Alvarez L, Neu J Tags: Cell Mol Life Sci Source Type: research

Concerns regarding Baksa B, Kovacs A, Bayasgalan T, Szentesi P, Koseghy A, Szucs P, Balazs P. Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus. Cell Molec. Life Sci. 2019-04-02.
PMID: 31570964 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 29, 2019 Category: Cytology Authors: Garcia-Rill E, Urbano FJ Tags: Cell Mol Life Sci Source Type: research

Zeta-crystallin: a moonlighting player in cancer.
Abstract Crystallins were firstly found as structural proteins of the eye lens. To this family belong proteins, such as ζ-crystallin, expressed ubiquitously, and endowed with enzyme activity. ζ-crystallin is a moonlighting protein endowed with two main different functions: (1) mRNA binding with stabilizing activity; (2) NADPH:quinone oxidoreductase. ζ-crystallin has been clearly demonstrated to stabilize mRNAs encoding proteins involved in renal glutamine catabolism during metabolic acidosis resulting in ammoniagenesis and bicarbonate ion production that concur to compensate such condition. &ze...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Lulli M, Nencioni D, Papucci L, Schiavone N Tags: Cell Mol Life Sci Source Type: research

Molecular and cellular evolution of corticogenesis in amniotes.
ell V Abstract The cerebral cortex varies dramatically in size and complexity between amniotes due to differences in neuron number and composition. These differences emerge during embryonic development as a result of variations in neurogenesis, which are thought to recapitulate modifications occurred during evolution that culminated in the human neocortex. Here, we review work from the last few decades leading to our current understanding of the evolution of neurogenesis and size of the cerebral cortex. Focused on specific examples across vertebrate and amniote phylogeny, we discuss developmental mechanisms regula...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Cárdenas A, Borrell V Tags: Cell Mol Life Sci Source Type: research

Molecular determinants of mesenchymal cell activation in fibroproliferative diseases.
Abstract Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic diseases represent a major cause of death in industrialized countries. Unfortunately, no curative treatments for these conditions are yet available, highlighting the critical need for a better fundamental understanding of molecular mechanisms that may be therapeutically tractable. The ultimate indispensable effector cells responsible for deposition of extracellular matrix proteins that comprise scars are mesenchymal cells, namely fibroblas...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Penke LR, Peters-Golden M Tags: Cell Mol Life Sci Source Type: research

Multifunctional nanomedicines for targeting epidermal growth factor receptor in colorectal cancer.
Abstract Systemic administration of chemotherapeutics by nanocarriers (NCs) functionalized with targeting agents provides a localized accumulation of drugs in the target tissues and cells. Advanced nanoscaled medicaments can enter into the tumor microenvironment (TME) and overcome the uniquely dysregulated biological settings of TME, including highly pressurized tumor interstitial fluid in an acidic milieu. Such multimodal nanomedicines seem to be one of the most effective treatment modalities against solid tumors such as colorectal cancer (CRC). To progress and invade, cancer cells overexpress various oncogenes a...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Akbarzadeh Khiavi M, Safary A, Barar J, Ajoolabady A, Somi MH, Omidi Y Tags: Cell Mol Life Sci Source Type: research

The Drosophila odorant-binding protein 28a is involved in the detection of the floral odour ß-ionone.
The Drosophila odorant-binding protein 28a is involved in the detection of the floral odour ß-ionone. Cell Mol Life Sci. 2019 Sep 28;: Authors: Gonzalez D, Rihani K, Neiers F, Poirier N, Fraichard S, Gotthard G, Chertemps T, Maïbèche M, Ferveur JF, Briand L Abstract Odorant-binding proteins (OBPs) are small soluble proteins that are thought to transport hydrophobic odorants across the aqueous sensillar lymph to olfactory receptors. A recent study revealed that OBP28a, one of the most abundant Drosophila OBPs, is not required for odorant transport, but acts in buffering rapid odour va...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Gonzalez D, Rihani K, Neiers F, Poirier N, Fraichard S, Gotthard G, Chertemps T, Maïbèche M, Ferveur JF, Briand L Tags: Cell Mol Life Sci Source Type: research

Global phosphoproteomic analysis of Ebola virions reveals a novel role for VP35 phosphorylation-dependent regulation of genome transcription.
Abstract Ebola virus (EBOV) causes severe human disease with a high case fatality rate. The balance of evidence implies that the virus circulates in bats. The molecular basis for host-viral interactions, including the role for phosphorylation during infections, is largely undescribed. To address this, and to better understand the biology of EBOV, the phosphorylation of EBOV proteins was analyzed in virions purified from infected monkey Vero-E6 cells and bat EpoNi/22.1 cells using high-resolution mass spectrometry. All EBOV structural proteins were detected with high coverage, along with phosphopeptides. Phosphoryl...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2019 Category: Cytology Authors: Ivanov A, Ramanathan P, Parry C, Ilinykh PA, Lin X, Petukhov M, Obukhov Y, Ammosova T, Amarasinghe GK, Bukreyev A, Nekhai S Tags: Cell Mol Life Sci Source Type: research

Insights into the non-mitotic functions of Aurora kinase A: more than just cell division.
Abstract AURKA is a serine/threonine kinase overexpressed in several cancers. Originally identified as a protein with multifaceted roles during mitosis, improvements in quantitative microscopy uncovered several non-mitotic roles as well. In physiological conditions, AURKA regulates cilia disassembly, neurite extension, cell motility, DNA replication and senescence programs. In cancer-like contexts, AURKA actively promotes DNA repair, it acts as a transcription factor, promotes cell migration and invasion, and it localises at mitochondria to regulate mitochondrial dynamics and ATP production. Here we review the non...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2019 Category: Cytology Authors: Bertolin G, Tramier M Tags: Cell Mol Life Sci Source Type: research

Purpurin modulates Tau-derived VQIVYK fibrillization and ameliorates Alzheimer's disease-like symptoms in animal model.
Abstract Neurofibrillary tangles of the Tau protein and plaques of the amyloid β peptide are hallmarks of Alzheimer's disease (AD), which is characterized by the conversion of monomeric proteins/peptides into misfolded β-sheet rich fibrils. Halting the fibrillation process and disrupting the existing aggregates are key challenges for AD drug development. Previously, we performed in vitro high-throughput screening for the identification of potent inhibitors of Tau aggregation using a proxy model, a highly aggregation-prone hexapeptide fragment 306VQIVYK311 (termed PHF6) derived from Tau. Here we have char...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2019 Category: Cytology Authors: Viswanathan GK, Shwartz D, Losev Y, Arad E, Shemesh C, Pichinuk E, Engel H, Raveh A, Jelinek R, Cooper I, Gosselet F, Gazit E, Segal D Tags: Cell Mol Life Sci Source Type: research

Fbxl17 is rearranged in breast cancer and loss of its activity leads to increased global O-GlcNAcylation.
Abstract In cancer, many genes are mutated by genome rearrangement, but our understanding of the functional consequences of this remains rudimentary. Here we report the F-box protein encoded by FBXL17 is disrupted in the region of the gene that encodes its substrate-binding leucine rich repeat (LRR) domain. Truncating Fbxl17 LRRs impaired its association with the other SCF holoenzyme subunits Skp1, Cul1 and Rbx1, and decreased ubiquitination activity. Loss of the LRRs also differentially affected Fbxl17 binding to its targets. Thus, genomic rearrangements in FBXL17 are likely to disrupt SCFFbxl17-regulated network...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2019 Category: Cytology Authors: Mason B, Flach S, Teixeira FR, Manzano Garcia R, Rueda OM, Abraham JE, Caldas C, Edwards PAW, Laman H Tags: Cell Mol Life Sci Source Type: research

The vertebrate tail: a gene playground for evolution.
Abstract The tail of all vertebrates, regardless of size and anatomical detail, derive from a post-anal extension of the embryo known as the tail bud. Formation, growth and differentiation of this structure are closely associated with the activity of a group of cells that derive from the axial progenitors that build the spinal cord and the muscle-skeletal case of the trunk. Gdf11 activity switches the development of these progenitors from a trunk to a tail bud mode by changing the regulatory network that controls their growth and differentiation potential. Recent work in the mouse indicates that the tail bud regul...
Source: Cellular and Molecular Life Sciences : CMLS - September 25, 2019 Category: Cytology Authors: Mallo M Tags: Cell Mol Life Sci Source Type: research

Targeting Hsp70 facilitated protein quality control for treatment of polyglutamine diseases.
Abstract The polyglutamine (polyQ) diseases are a group of nine fatal, adult-onset neurodegenerative disorders characterized by the misfolding and aggregation of mutant proteins containing toxic expansions of CAG/polyQ tracts. The heat shock protein 90 and 70 (Hsp90/Hsp70) chaperone machinery is a key component of cellular protein quality control, playing a role in the regulation of folding, aggregation, and degradation of polyQ proteins. The ability of Hsp70 to facilitate disaggregation and degradation of misfolded proteins makes it an attractive therapeutic target in polyQ diseases. Genetic studies have demonstr...
Source: Cellular and Molecular Life Sciences : CMLS - September 23, 2019 Category: Cytology Authors: Davis AK, Pratt WB, Lieberman AP, Osawa Y Tags: Cell Mol Life Sci Source Type: research

Bacterial stress defense: the crucial role of ribosome speed.
Abstract In nature, bacteria are constantly adapting to various stressful conditions. Timely activation of stress response programs is crucial for bacteria to smoothly survive under stressful conditions. Stress response, demanding the de novo synthesis of many defense proteins, is generally activated at the transcriptional level by specific regulators. However, the effect of the global protein translational status on stress response has been largely overlooked. The translational capacity is limited by the number of translating ribosomes and the translational elongation rate. Recent work has shown that certain envi...
Source: Cellular and Molecular Life Sciences : CMLS - September 23, 2019 Category: Cytology Authors: Zhu M, Dai X Tags: Cell Mol Life Sci Source Type: research

Deciphering structure, function and mechanism of lysine acetyltransferase HBO1 in protein acetylation, transcription regulation, DNA replication and its oncogenic properties in cancer.
Abstract HBO1 complexes are major acetyltransferase responsible for histone H4 acetylation in vivo, which belongs to the MYST family. As the core catalytic subunit, HBO1 consists of an N-terminal domain and a C-terminal MYST domain that are in charge of acetyl-CoA binding and acetylation reaction. HBO1 complexes are multimeric and normally consist of two native subunits MEAF6, ING4 or ING5 and two kinds of cofactors as chromatin reader: Jade-1/2/3 and BRPF1/2/3. The choices of subunits to form the HBO1 complexes provide a regulatory switch to potentiate its activity between histone H4 and H3 tails. Thus, HBO1 comp...
Source: Cellular and Molecular Life Sciences : CMLS - September 17, 2019 Category: Cytology Authors: Lan R, Wang Q Tags: Cell Mol Life Sci Source Type: research

Evidence for miR-548c-5p regulation of FOXC2 transcription through a distal genomic target site in human podocytes.
Abstract Podocytes are highly differentiated epithelial cells outlining the glomerular vessels. FOXC2 is a transcription factor essential for inducing podocyte differentiation, development and maturation, and is considered to be the earliest podocyte marker. miRNA prediction analysis revealed a full-length target site for the primate-specific miR-548c-5p at a genomic region > 8 kb upstream of FOXC2. We hypothesised that the transcription rates of FOXC2 during podocyte differentiation might be tuned by miR-548c-5p through this target site. Experiments were performed with cultured human podocyt...
Source: Cellular and Molecular Life Sciences : CMLS - September 16, 2019 Category: Cytology Authors: Christofides A, Papagregoriou G, Dweep H, Makrides N, Gretz N, Felekkis K, Deltas C Tags: Cell Mol Life Sci Source Type: research

What is strain in neurodegenerative diseases?
Abstract Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by the aggregation of misfolded proteins, including Aβ, tau and α-synuclein. It is well recognized that these misfolded proteins are able to self-propagate and spread throughout the nervous system and cause neuronal injury in a way that resembles prion disease. These disease-specific misfolded proteins demonstrate unique features, including the seeding barrier, the conformational memory effect, strain selection and strain evolution, based on the presence of various strains. However, the accurate d...
Source: Cellular and Molecular Life Sciences : CMLS - September 16, 2019 Category: Cytology Authors: Tian Y, Meng L, Zhang Z Tags: Cell Mol Life Sci Source Type: research

Current perspective on the regulation of FOXO4 and its role in disease progression.
Abstract Forkhead box O4 (FOXO4) is a member of the FOXO family that regulates a number of genes involved in metabolism, cell cycle, apoptosis, and cellular homeostasis via transcriptional activity. It also mediates cell responses to oxidative stress and treatment with antitumor agents. The expression of FOXO4 is repressed by microRNAs in multiple cancer cells, while FOXO4 function is regulated by post-translational modifications and interaction with other proteins. The deregulation of FOXO4 is closely linked to the progression of several types of cancer, senescence, and other diseases. In this review, we present ...
Source: Cellular and Molecular Life Sciences : CMLS - September 15, 2019 Category: Cytology Authors: Liu W, Li Y, Luo B Tags: Cell Mol Life Sci Source Type: research

Auditory function and dysfunction: estrogen makes a difference.
oix L Abstract Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that ar...
Source: Cellular and Molecular Life Sciences : CMLS - September 13, 2019 Category: Cytology Authors: Delhez A, Lefebvre P, Péqueux C, Malgrange B, Delacroix L Tags: Cell Mol Life Sci Source Type: research

Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBP α and canonical Wnt signaling.
Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling. Cell Mol Life Sci. 2019 Sep 12;: Authors: Qi Q, Wang Y, Wang X, Yang J, Xie Y, Zhou J, Li X, Wang B Abstract Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and establishe...
Source: Cellular and Molecular Life Sciences : CMLS - September 11, 2019 Category: Cytology Authors: Qi Q, Wang Y, Wang X, Yang J, Xie Y, Zhou J, Li X, Wang B Tags: Cell Mol Life Sci Source Type: research

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications.
Abstract Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of co...
Source: Cellular and Molecular Life Sciences : CMLS - September 8, 2019 Category: Cytology Authors: Totland MZ, Rasmussen NL, Knudsen LM, Leithe E Tags: Cell Mol Life Sci Source Type: research

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways.
This study demonstrates that Toxoplasma hijacks a new epigenetic initiator, UHRF1, through an early event initiated by the ROP16 parasite kinase. PMID: 31492965 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Sabou M, Doderer-Lang C, Leyer C, Konjic A, Kubina S, Lennon S, Rohr O, Viville S, Cianférani S, Candolfi E, Pfaff AW, Brunet J Tags: Cell Mol Life Sci Source Type: research

The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation.
In this study, we demonstrated that DCAF13 stimulates the meiotic resumption-coupled activation of protein synthesis in oocytes, partially by maintaining the activity of PI3K signaling pathway. CRL4-DCAF13 targets the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Dcaf13 knockout in oocytes caused decreased CDK1 activity and impaired meiotic cell cycle progression and chromosome condensation defects. As a result, chromosomes fail to be aligned at the spindle equatorial plate, the spindle assembly checkpoint is activated, and most Dcaf13 nu...
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Zhang J, Zhang YL, Zhao LW, Pi SB, Zhang SY, Tong C, Fan HY Tags: Cell Mol Life Sci Source Type: research

Stoichiometry and regulation network of Bcl-2 family complexes quantified by live-cell FRET assay.
Abstract The stoichiometry and affinity of Bcl-2 family complexes are essential information for understanding how their interactome network is orchestrated to regulate mitochondrial permeabilization and apoptosis. Based on over-expression model system, FRET analysis was used to quantify the protein-protein interactions among Bax, Bcl-xL, Bad and tBid in healthy and apoptotic cells. Our data indicate that the stoichiometry and affinity of Bcl-2 complexes are dependent on their membrane environment. Bcl-xL, Bad and tBid can form hetero-trimers in mitochondria. Bcl-xL binds preferentially to Bad, then to tBid and Bax...
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Yang F, Qu W, Du M, Mai Z, Wang B, Ma Y, Wang X, Chen T Tags: Cell Mol Life Sci Source Type: research

MicroRNA-24-3p regulates neuronal differentiation by controlling hippocalcin expression.
Abstract Hippocalcin (HPCA) is a neuron-specific calcium-binding protein predominantly expressed in the nervous system. In the present study, we demonstrate that HPCA regulates neuronal differentiation in SH-SY5Y cells. We observed that the expression level of HPCA was increased during neuronal differentiation. Depletion of HPCA inhibited both neurite outgrowth and synaptophysin (SYP) expression, whereas overexpression of HPCA enhanced neuronal differentiation. Interestingly, we also found that the expression of HPCA mRNA was modulated by miR-24-3p. Using a dual-luciferase assay, we showed that co-transfection of ...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Kang MJ, Park SY, Han JS Tags: Cell Mol Life Sci Source Type: research

Structural and functional analysis of "non-smelly" proteins.
Structural and functional analysis of "non-smelly" proteins. Cell Mol Life Sci. 2019 Sep 05;: Authors: Yan J, Cheng J, Kurgan L, Uversky VN Abstract Cysteine and aromatic residues are major structure-promoting residues. We assessed the abundance, structural coverage, and functional characteristics of the "non-smelly" proteins, i.e., proteins that do not contain cysteine residues (C-depleted) or cysteine and aromatic residues (CFYWH-depleted), across 817 proteomes from all domains of life. The analysis revealed that although these proteomes contained significant levels of the C-depl...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Yan J, Cheng J, Kurgan L, Uversky VN Tags: Cell Mol Life Sci Source Type: research

Sialic acid-binding immunoglobulin-like lectins (Siglecs) detect self-associated molecular patterns to regulate immune responses.
i A Abstract The mammalian immune system evolved to tightly regulate the elimination of pathogenic microbes and neoplastic transformed cells while tolerating our own healthy cells. Here, we summarize experimental evidence for the role of Siglecs-in particular CD33-related Siglecs-as self-receptors and their sialoglycan ligands in regulating this balance between recognition of self and non-self. Sialoglycans are found in the glycocalyx and extracellular fluids and matrices of all mammalian cells and can be considered as self-associated molecular patterns (SAMPs). We also provide an overview of the known interaction...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2019 Category: Cytology Authors: Läubli H, Varki A Tags: Cell Mol Life Sci Source Type: research

Insights from Drosophila on mitochondrial complex I.
Abstract NADH:ubiquinone oxidoreductase, more commonly referred to as mitochondrial complex I (CI), is the largest discrete enzyme of the oxidative phosphorylation system (OXPHOS). It is localized to the mitochondrial inner membrane. CI oxidizes NADH generated from the tricarboxylic acid cycle to NAD+, in a series of redox reactions that culminates in the reduction of ubiquinone, and the transport of protons from the matrix across the inner membrane to the intermembrane space. The resulting proton-motive force is consumed by ATP synthase to generate ATP, or harnessed to transport ions, metabolites and proteins int...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2019 Category: Cytology Authors: Rhooms SK, Murari A, Goparaju NSV, Vilanueva M, Owusu-Ansah E Tags: Cell Mol Life Sci Source Type: research

Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.
Abstract Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2CreER/+ Foxg1loxp/loxp mice and Lgr5-EGFPCreER/+ Foxg1loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2019 Category: Cytology Authors: Zhang S, Zhang Y, Dong Y, Guo L, Zhang Z, Shao B, Qi J, Zhou H, Zhu W, Yan X, Hong G, Zhang L, Zhang X, Tang M, Zhao C, Gao X, Chai R Tags: Cell Mol Life Sci Source Type: research

Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular Ca2+ signals and nitric oxide release in human brain microvascular endothelial cells.
Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-D-aspartate receptors to mediate extracellular Ca2+ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial Ca2+ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular Ca2+ signals follo...
Source: Cellular and Molecular Life Sciences : CMLS - August 30, 2019 Category: Cytology Authors: Negri S, Faris P, Pellavio G, Botta L, Orgiu M, Forcaia G, Sancini G, Laforenza U, Moccia F Tags: Cell Mol Life Sci Source Type: research