Molecular architecture of postsynaptic Interactomes.
Abstract The postsynaptic density (PSD) plays an essential role in the organization of the synaptic signaling machinery. It contains a set of core scaffolding proteins that provide the backbone to PSD protein-protein interaction networks (PINs). These core scaffolding proteins can be seen as three principal layers classified by protein family, with DLG proteins being at the top, SHANKs along the bottom, and DLGAPs connecting the two layers. Early studies utilizing yeast two hybrid enabled the identification of direct protein-protein interactions (PPIs) within the multiple layers of scaffolding proteins. More recen...
Source: Cellular Signalling - September 14, 2020 Category: Cytology Authors: Wilkinson B, Coba MP Tags: Cell Signal Source Type: research

Cell death signalling in virus infection.
Abstract Apoptosis, necroptosis and pyroptosis represent three major regulated cell death modalities. Apoptosis features cell shrinkage, nuclear fragmentation and cytoplasm-blebbing. Necroptosis and pyroptosis exhibit osmotic imbalances in the cell accompanied by early membrane ruptures, which morphologically resembles necrosis. Importantly, these two lytic cell death forms facilitate the release of damage associated molecular patterns into the extracellular space leading to inflammatory response. Whereas, during apoptosis, the membrane integrity is preserved and the apoptotic cell is removed by neighbouring cells...
Source: Cellular Signalling - September 12, 2020 Category: Cytology Authors: Imre G Tags: Cell Signal Source Type: research

Molecular pathways in peritoneal fibrosis.
Abstract Peritoneal dialysis (PD) is a renal replacement therapy for patients with end-stage renal disease that is equivalent to hemodialysis with respect to adequacy, mortality, and other outcome parameters, yet providing superior quality-of-life measures and cost savings. However, long-term usage of the patient's peritoneal membrane as a dialyzer filter is unphysiological and leads to peritoneal fibrosis, which is a major factor of patient morbidity and PD technique failure, resulting in a transfer to hemodialysis or death. Peritoneal fibrosis pathophysiology involves chronic inflammation and the fibrotic proces...
Source: Cellular Signalling - September 11, 2020 Category: Cytology Authors: Balzer MS Tags: Cell Signal Source Type: research

Silencing TTTY15 mitigates hypoxia-induced mitochondrial energy metabolism dysfunction and cardiomyocytes apoptosis via TTTY15/let-7i-5p and TLR3/NF- κB pathways.
Silencing TTTY15 mitigates hypoxia-induced mitochondrial energy metabolism dysfunction and cardiomyocytes apoptosis via TTTY15/let-7i-5p and TLR3/NF-κB pathways. Cell Signal. 2020 Sep 11;:109779 Authors: Zhang H, Zou X, Liu F Abstract Noncoding RNAs are interweaved in pathological processes in myocardial ischemia (MI), such as long noncoding RNA (lncRNA) and microRNAs (miRNAs). The aim of this study was to figure out the role of Testis-specific transcript Y-linked 15 (TTTY15) and let-7i-5p in cell model of MI in cardiomyocytes. Hypoxia-induced cell injury was assessed by Cell counting kit 8 assa...
Source: Cellular Signalling - September 11, 2020 Category: Cytology Authors: Zhang H, Zou X, Liu F Tags: Cell Signal Source Type: research

TRIM32 regulates mitochondrial mediated ROS levels and sensitizes the oxidative stress induced cell death.
Abstract Emerging evidence suggests that ubiquitin mediated post translational modification is a critical regulatory process involved in diverse cellular pathways including cell death. During ubiquitination, E3 ligases recognize target proteins and determine the topology of ubiquitin chains. Recruitment of E3 ligases to targets proteins under stress conditions including oxidative stress and their implication in cell death have not been systemically explored. In the present study, we characterized the role of TRIM32 as an E3 ligase in regulation of oxidative stress induced cell death. TRIM32 is ubiquitously express...
Source: Cellular Signalling - September 9, 2020 Category: Cytology Authors: Prajapati P, Gohel D, Shinde A, Roy M, Singh K, Singh R Tags: Cell Signal Source Type: research

The promoting role of lysosome-localized c-Src in autophagosome-lysosome fusion.
Abstract Src-family kinases (SFKs), such as c-Src, Lyn and Fyn, belong to non-receptor-type tyrosine kinases and play key roles in cell proliferation, adhesion, and migration. SFKs are anchored to the plasma membrane, Golgi membranes and lysosomal membranes through lipid modifications. Although the functions of SFKs being localized to the plasma membrane are intensively studied, those of SFKs being localized to organelle membranes are poorly understood. Here, we show that, among SFKs, c-Src in particular is involved in a decrease in the amount of LC3-II. c-Src and non-palmitoylated Lyn [Lyn(C3S) (cysteine-3 &rar...
Source: Cellular Signalling - September 8, 2020 Category: Cytology Authors: Suzuki K, Honda T, Akatsu A, Yamaguchi N, Yamaguchi N Tags: Cell Signal Source Type: research

Clostridium perfringens phospholipase C impairs innate immune response by inducing integrated stress response and mitochondrial-induced epigenetic modifications.
Abstract Clostridium perfringens, a rod-shaped, gram-positive, anaerobic, spore-forming bacterium is one of the most widely occurring bacterial pathogens, associated with a spectrum of diseases in humans. A major virulence factor during its infection is the enzyme phospholipase C encoded by the plc gene, known as Clostridium perfringens phospholipase C (CpPLC). The present study was designed to understand the role of CpPLC in inducing survival mechanisms and mitochondrial-induced epigenetic changes in a human lymphocyte cell culture model. Following exposure to CpPLC, a significant generation of mitochondrial reac...
Source: Cellular Signalling - September 8, 2020 Category: Cytology Authors: Bunkar N, Sharma J, Chouksey A, Kumari R, Gupta PK, Tiwari R, Lodhi L, Srivastava RK, Bhargava A, Mishra PK Tags: Cell Signal Source Type: research

Nelfinavir inhibits human DDI2 and potentiates cytotoxicity of proteasome inhibitors.
Abstract Proteasome inhibitors (PIs) are currently used in the clinic to treat cancers such as multiple myeloma (MM). However, cancer cells often rapidly develop drug resistance towards PIs due to a compensatory mechanism mediated by nuclear factor erythroid 2 like 1 (NFE2L1) and aspartic protease DNA damage inducible 1 homolog 2 (DDI2). Following DDI2-mediated cleavage, NFE2L1 is able to induce transcription of virtually all proteasome subunit genes. Under normal condition, cleaved NFE2L1 is constantly degraded by proteasome, whereas in the presence of PIs, it accumulates and induces proteasome synthesis which in...
Source: Cellular Signalling - September 8, 2020 Category: Cytology Authors: Gu Y, Wang X, Wang Y, Wang Y, Li J, Yu FX Tags: Cell Signal Source Type: research

Milestones in the development and implementation of FRET-based sensors of intracellular signals: A biological perspective of the history of FRET.
Abstract Fӧrster resonance energy transfer (FRET) has been described for more than a century. FRET has become a mainstay for the study of protein localization in living cells and tissues. It has also become widely used in the fields that comprise cellular signaling. FRET-based probes have been developed to monitor second messenger signals, the phosphorylation state of peptides and proteins, and subsequent cellular responses. Here, we discuss the milestones that led to FRET becoming a widely used tool for the study of biological systems: the theoretical description of FRET, the insight to use FRET as a molecular r...
Source: Cellular Signalling - September 5, 2020 Category: Cytology Authors: Deal J, Pleshinger DJ, Johnson SC, Leavesley SJ, Rich TC Tags: Cell Signal Source Type: research

IL-36 family cytokines in protective versus destructive inflammation.
t A Abstract The IL-1 family of cytokines and receptors are critical regulators of inflammation. Within the IL-1 family and in contrast to its IL-1 and IL-18 subfamilies, the IL-36 subfamily is still poorly characterized. Three pro-inflammatory agonists IL-36α, IL-36β, IL-36γ, one IL-36 receptor (IL-1R6) antagonist, IL-36RA, and one putative IL-1R6 antagonist, IL-38, have been grouped into the IL-36 cytokine subfamily. IL-36 agonists signal through a common receptor complex to serve as early triggers of inflammatory responses by activating and cross-regulating a number of inflammatory pathways inc...
Source: Cellular Signalling - September 5, 2020 Category: Cytology Authors: Han Y, Huard A, Mora J, da Silva P, Brüne B, Weigert A Tags: Cell Signal Source Type: research

Activation of autophagy inhibits epithelial to mesenchymal transition process of human lens epithelial cells induced by high glucose conditions.
Abstract Subcapsular cataracts are common phenotype of diabetic cataracts, and abnormal lens epithelial cells (LECs) under the lens capsules have been considered to involve in the pathogenesis. Our previous studies have shown that the epithelial to mesenchymal transition (EMT), which is responsible for the LECs to lose their original polarity and tight junctions, occurs in a diabetic cataract mouse model. Autophagy is known to function in the EMT process in multiple tissues. However, the relationship between autophagy and EMT process in LECs has not yet been fully demonstrated. We found that high glucose retreatme...
Source: Cellular Signalling - September 4, 2020 Category: Cytology Authors: Li J, Ye W, Xu W, Chang T, Zhang L, Ma J, Pei R, He M, Zhou J Tags: Cell Signal Source Type: research

Exosomal vesicles enhance immunosuppression in chronic inflammation: Impact in cellular senescence and the aging process.
Abstract Exosomes represent an evolutionarily conserved signaling pathway which can act as an alarming mechanism in responses to diverse stresses, e.g. chronic inflammation activates the budding of exosomal vesicles in both immune and non-immune cells. Exosomes can contain both pro- and anti-inflammatory cargos but in chronic inflammation, exosomes mostly carry immunosuppressive cargos, e.g. enzymes and miRNAs. The aging process is associated with chronic low-grade inflammation and the accumulation of pro-inflammatory senescent cells into tissues. There is clear evidence that aging increases the number of exosomes...
Source: Cellular Signalling - September 4, 2020 Category: Cytology Authors: Salminen A, Kaarniranta K, Kauppinen A Tags: Cell Signal Source Type: research

Signalling pathways linking cysteine cathepsins to adverse cardiac remodelling.
Abstract Adverse cardiac remodelling clinically manifests as deleterious changes to heart architecture (size, mass and geometry) and function. These changes, which include alterations to ventricular wall thickness, chamber dilation and poor contractility, are important because they progressively drive patients with cardiac disease towards heart failure and are associated with poor prognosis. Cysteine cathepsins contribute to key signalling pathways involved in adverse cardiac remodelling including synthesis and degradation of the cardiac extracellular matrix (ECM), cardiomyocyte hypertrophy, impaired cardiomyocyte...
Source: Cellular Signalling - September 3, 2020 Category: Cytology Authors: O'Toole D, Zaeri AAI, Nicklin SA, French AT, Loughrey CM, Martin TP Tags: Cell Signal Source Type: research

KLF5-mediated COX2 upregulation contributes to tumorigenesis driven by PTEN deficiency.
Abstract Tumor suppressor gene PTEN is frequently mutated in a wide variety of cancers. However, the downstream targets or signal transduction pathways of PTEN remain not fully understood. By analyzing Pten-null mouse embryonic fibroblasts (MEFs) cell lines and their isogenic counterparts, we showed that loss of PTEN led to increased cyclooxygenase2 (COX2) expression in an AKT-independent manner. Moreover, we demonstrated that PTEN deficiency promotes the transcription of COX2 via upregulation of the transcription factor Krüppel-like factor 5 (KLF5). Knocked down the expression of COX2 suppressed proliferatio...
Source: Cellular Signalling - September 2, 2020 Category: Cytology Authors: Zhang L, Wu Y, Wu J, Zhou M, Li D, Wan X, Jin F, Wang Y, Lin W, Zha X, Liu Y Tags: Cell Signal Source Type: research

Ubiquitin ligase TRUSS augments the expression of interleukin-10 via proteasomal processing of NF- κB1/p105 to NF-κB/p50.
Ubiquitin ligase TRUSS augments the expression of interleukin-10 via proteasomal processing of NF-κB1/p105 to NF-κB/p50. Cell Signal. 2020 Sep 01;:109766 Authors: Jamal A, Husein A, Bihari C, Kumar V Abstract The NF-κB/Rel family of transcription factors that play critical roles in a variety of cellular processes. Their production in the cell and physiological activation are tightly regulated. The proteasomal processing of inactive NF-κB1/p105 to active p50, with an anti-inflammatory role, is not well characterized. Here we show that ubiquitin ligase TRUSS is a mediator of tran...
Source: Cellular Signalling - September 1, 2020 Category: Cytology Authors: Jamal A, Husein A, Bihari C, Kumar V Tags: Cell Signal Source Type: research

Corrigendum to "A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1" [Cell Signal. 2020 Feb;66:109462. doi: 10.1016/j.cellsig.2019.109462].
Corrigendum to "A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1" [Cell Signal. 2020 Feb;66:109462. doi: 10.1016/j.cellsig.2019.109462]. Cell Signal. 2020 Sep;73:109715 Authors: Liang Y, Rong X, Luo Y, Li P, Han Q, Wei L, Wang E PMID: 32709464 [PubMed - in process] (Source: Cellular Signalling)
Source: Cellular Signalling - July 28, 2020 Category: Cytology Authors: Liang Y, Rong X, Luo Y, Li P, Han Q, Wei L, Wang E Tags: Cell Signal Source Type: research

GPCR mediated control of calcium dynamics: A systems perspective.
This article is the first study in reviewing the network structures underlying GPCR signal transduction that control downstream [Cac2+]-oscillations. The central theme of this paper is to present the biochemical pathways, as well as molecular mechanisms underlying the GPCR-mediated Ca2+-dynamics in order to facilitate a better understanding of how agonist concentration is encoded by Ca2+-signaling. Moreover, we present the GPCR targeting drugs that are relevant for treating cardiac, respiratory, and neuro-diseases along with agonist concentration encoding of Ca2+-response corresponding to Gαq, Gαs, and Gα...
Source: Cellular Signalling - July 22, 2020 Category: Cytology Authors: Dhyani V, Gare S, Gupta RK, Swain S, Venkatesh KV, Giri L Tags: Cell Signal Source Type: research

Liver X receptor inhibits the growth of hepatocellular carcinoma cells via regulating HULC/miR-134-5p/FOXM1 axis.
In this study, we found that LXR inhibited HCC cell growth by downregulating HULC, and LXRα (but not LXRβ) caused HULC downregulation. Luciferase reporter assays showed that LXR suppressed transcriptional activity of HULC gene promoter, and chromatin immunoprecipitation assays revealed that LXRα (but not LXRβ) bound to HULC promoter region. Furthermore, LXR increased miR-134-5p while decreased FOXM1 by reducing HULC. Additionally, HULC upregulated FOXM1 via sequestrating miR-134-5p, and miR-134-5p downregulated FOXM1 by targeting 3'-UTR of its mRNA. The in vivo experiments showed that LXR repressed th...
Source: Cellular Signalling - July 22, 2020 Category: Cytology Authors: He J, Yang T, He W, Jiang S, Zhong D, Xu Z, Wei Q, Zhang Y, Shi C Tags: Cell Signal Source Type: research

Drugs targeting various stages of the SARS-CoV-2 life cycle: Exploring promising drugs for the treatment of Covid-19.
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA virus that causes the potentially lethal Covid-19 respiratory tract infection. It does so by binding to host cell angiotensin converting enzyme 2 (ACE2) receptors, leading to endocytosis with the receptor, and subsequently using the host cell's machinery to replicate copies of itself and invade new cells. The extent of the spread of infection in the body is dependent on the pattern of ACE2 expression and overreaction of the immune system. Additionally, by inducing an imbalance in the renin-angiotensin...
Source: Cellular Signalling - July 22, 2020 Category: Cytology Authors: Poduri R, Joshi G, Jagadeesh G Tags: Cell Signal Source Type: research

ANXA2P2/miR-9/LDHA axis regulates Warburg effect and affects glioblastoma proliferation and apoptosis.
CONCLUSIONS: In conclusion, ANXA2P2/miR-9/LDHA axis modulates the aerobic glycolysis progression in glioma cells, therefore affecting glioma cell proliferation. PMID: 32707073 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - July 21, 2020 Category: Cytology Authors: Du P, Liao Y, Zhao H, Zhang J, Ti M, Shi K, Mu K Tags: Cell Signal Source Type: research

miR-29b-3p protects cardiomyocytes against endotoxin-induced apoptosis and inflammatory response through targeting FOXO3A.
Abstract Cardiac dysfunction represents a main component of death induced by sepsis in critical care units. And microRNAs (miRNAs) have been reported as important modulators or biomarkers of sepsis. However, the molecular detail of miRNAs involved in septic cardiac dysfunction remains unclear. Here we showed that endotoxin (lipopolysaccharide, LPS) significantly down-regulated expression of miR-29b-3p in heart. Increased expression of miR-29b-3p by lentivirus improved cardiac function and attenuated damage of cardiac induced by LPS in mice. Furthermore, overexpression or knockdown of miR-29b-3p showed its crucial ...
Source: Cellular Signalling - July 21, 2020 Category: Cytology Authors: Li Z, Yi N, Chen R, Meng Y, Wang Y, Liu H, Cao W, Hu Y, Gu Y, Tong C, Lu M, Li L, Peng L Tags: Cell Signal Source Type: research

CD34 positive cells isolated from traumatized human skeletal muscle require the CD34 protein for multi-potential differentiation.
Abstract The CD34 protein is regarded as a marker of stem cells from multiple origins. Recently a mesenchymal progenitor CD34 positive cell identified from traumatized human skeletal muscle demonstrates differentiation capability into vascular endothelial cells, osteoblasts and adipocytes. Here they were treated with a small inhibitory RNA for CD34, which significantly reduced the cellular level of the CD34 protein. These treated cells had a reduced capacity to proliferate, and migrate. They were both unable to differentiation down multiple pathways and to undergo vascular endothelial differentiation as reflected ...
Source: Cellular Signalling - July 20, 2020 Category: Cytology Authors: Wolcott KM, Woodard GE Tags: Cell Signal Source Type: research

Drosophila Uev1a is dually required for Ben-dependent DNA-damage response and fly mobility.
Abstract K63-linked polyubiquitination requires the ubiquitin-conjugating enzyme Ubc13 and a Ubc/E2 variant Uev. Lower eukaryotic organisms contain one UEV gene required for DNA-damage tolerance, while vertebrates and higher plants contain multiple UEV genes with distinct functions. In contrast, Drosophila contains only one UEV gene designated dUev1a. Here we report that dUev1a forms a stable heterodimer with Ben, the Drosophila Ubc13 ortholog, that dUev1a-F15E completely abolishes the interaction, and that a conserved dUev1a-F15Y substitution severely reduces its interaction with Ben. dUev1a functionally rescues ...
Source: Cellular Signalling - July 20, 2020 Category: Cytology Authors: Bai Z, Wei M, Li Z, Xiao W Tags: Cell Signal Source Type: research

Activation of TNFR1 and TLR4 following oxygen glucose deprivation promotes mitochondrial fission in C6 astroglial cells.
Abstract Astrocytes have emerged as active players in the innate immune response triggered by various types of insults. Recent literature suggests that mitochondria are key participants in innate immunity. The present study investigates the role of ischemia-induced innate immune response on p65/PGC-1α mediated mitochondrial dynamics in C6 astroglial cells. OGD conditions induced astroglial differentiation in C6 cells and increased the expression of hypoxia markers; HIF-1α, HO-1 and Cox4i2. OGD conditions resulted in induction of innate immune response in terms of expression of TNFR1 and TLR4 along with...
Source: Cellular Signalling - July 18, 2020 Category: Cytology Authors: Halder A, Yadav K, Aggarwal A, Singhal N, Sandhir R Tags: Cell Signal Source Type: research

Phosphorylation within the bipartite NLS alters the localization and toxicity of the ER stress response factor DDIT3/CHOP.
Abstract Regulated nuclear-cytoplasmic trafficking is a well-established mechanism utilized by cells to regulate adaptive and maladaptive responses to acute oxidant stress. Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. We show through functional analyses that CHOP contains a conserved, compound pat4/bipartite nuclear localization signal within the basic DNA-binding domain. Using phylogenetic analyses and ...
Source: Cellular Signalling - July 13, 2020 Category: Cytology Authors: Bartko JC, Li Y, Sun Z, Halterman MW Tags: Cell Signal Source Type: research

Uev1A amino terminus stimulates poly-ubiquitin chain assembly and is required for NF- κB activation.
Uev1A amino terminus stimulates poly-ubiquitin chain assembly and is required for NF-κB activation. Cell Signal. 2020 Jul 10;:109712 Authors: Wu Z, Andersen PL, Moraes T, McKenna SA, Zhang Y, Zhang W, Ellison MJ, Xiao W Abstract The ubiquitin (Ub)-conjugating enzyme variants (Uev) Uev1A and Mms2 interact with Ubc13 to form heterodimeric complexes with different biological functions. Uev1A-Ubc13 is involved in NF-κB activation while Mms2-Ubc13 is required for the DNA-damage response. The structural comparison of the core domains of these two Uevs reveals no obvious difference, suggesting th...
Source: Cellular Signalling - July 10, 2020 Category: Cytology Authors: Wu Z, Andersen PL, Moraes T, McKenna SA, Zhang Y, Zhang W, Ellison MJ, Xiao W Tags: Cell Signal Source Type: research

MYCT1 inhibits the EMT and migration of laryngeal cancer cells via the SP1/miR-629-3p/ESRP2 pathway.
In this study, we aimed to explore the mechanism of MYCT1 in the epithelial-mesenchymal transition (EMT) and migration of laryngeal cancer cells. We found that MYCT1 significantly decreased the expression of miR-629-3p but increased the expression of ESRP2 in laryngeal cancer cells. The expression of miR-629-3p and ESRP2 in laryngeal cancer tissues showed significantly positive and negative correlations with patient metastasis, respectively. miR-629-3p was confirmed to repress the expression of ESRP2 by targeting its 3'UTR. SP1 was verified to be a direct transcription factor for miR-629-3p and a downstream target of MYCT1...
Source: Cellular Signalling - July 10, 2020 Category: Cytology Authors: Yue PJ, Sun YY, Li YH, Xu ZM, Fu WN Tags: Cell Signal Source Type: research

Long non-coding RNA Linc00092 inhibits cardiac fibroblast activation by altering glycolysis in an ERK-dependent manner.
Abstract AIMS: Cardiac fibroblast (CF) activation is the key event for cardiac fibrosis. The role of glycolysis and the glycolysis-related lncRNAs in CF activation are unknown. Thus, we aimed to investigate the role of glycolysis in CF activation and to identify the glycolysis-related lncRNAs involved. MAIN METHODS: Glycolysis-related lncRNAs were searched and their expression profiles were validated in activated human CF (HCF) and human failing heart tissues. Expression of the target lncRNA was manipulated to determine its effects on HCF activation and glycolysis. The underlying mechanisms of lncRNA-dependen...
Source: Cellular Signalling - July 9, 2020 Category: Cytology Authors: Chen ZT, Zhang HF, Wang M, Wang SH, Wen ZZ, Gao QY, Wu MX, Liu WH, Xie Y, Mai JT, Yang Y, Wang JF, Chen YX Tags: Cell Signal Source Type: research

Chondroitin sulfate proteoglycan-5 forms perisynaptic matrix assemblies in the adult rat cortex.
A, Hanics J Abstract Composition of the brain extracellular matrix changes in time as maturation proceeds. Chondroitin sulfate proteoglycan 5 (CSPG-5), also known as neuroglycan C, has been previously associated to differentiation since it shapes neurite growth and synapse forming. Here, we show that this proteoglycan persists in the postnatal rat brain, and its expression is higher in cortical regions with plastic properties, including hippocampus and the medial prefrontal cortex at the end of the second postnatal week. Progressively accumulating after birth, CSPG-5 typically concentrates around glutamatergic and...
Source: Cellular Signalling - July 9, 2020 Category: Cytology Authors: Pintér A, Hevesi Z, Zahola P, Alpár A, Hanics J Tags: Cell Signal Source Type: research

Blocking NFATc3 ameliorates azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer in mice via the inhibition of inflammatory responses and epithelial-mesenchymal transition.
In conclusion, NFATc3 was involved in the pathogenesis of experimental UC-CRC and NFATc3 knockdown ameliorated experimental UC-CRC progression via the inhibition of inflammatory responses and EMT. NFATc3 mediated the inhibitory effects of miR-370-3p on CRC cells proliferation and EMT. Targeting NFATc3 may be effective in treating UC-CRC. PMID: 32653643 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - July 9, 2020 Category: Cytology Authors: Lin Y, Koumba MH, Qu S, Wang D, Lin L Tags: Cell Signal Source Type: research

Pathway identification through transcriptome analysis.
Abstract Systems-based, agnostic approaches focusing on transcriptomics data have been employed to understand the pathogenesis of polycystic kidney diseases (PKD). While multiple signaling pathways, including Wnt, mTOR and G-protein-coupled receptors, have been implicated in late stages of disease, there were few insights into the transcriptional cascade immediately downstream of Pkd1 inactivation. One of the consistent findings has been transcriptional evidence of dysregulated metabolic and cytoskeleton remodeling pathways. Recent technical developments, including bulk and single-cell RNA sequencing technologies ...
Source: Cellular Signalling - July 7, 2020 Category: Cytology Authors: Terabayashi A, Germino GG, Menezes LF Tags: Cell Signal Source Type: research

MeCP2 inactivation of LncRNA GAS5 triggers cardiac fibroblasts activation in cardiac fibrosis.
In this study, we explored MeCP2 inactivation of LncRNA GAS5 leads to down regulation of LncRNA GAS5 expression in cardiac fibrosis. Gain and loss function of LncRNA GAS5 and MeCP2 was analyzed. The expression of LncRNA GAS5 was significantly decreased in cardiac fibrosis tissues, while MeCP2 was significantly increased. Moreover, the expression of MeCP2 was increased in TGF-β1 induced cardiac fibroblasts, while the expression of LncRNA GAS5 was decreased. Down regulation of LncRNA GAS5 resulted in increasing cellular proliferation. In contrast, exogenous over expression of LncRNA GAS5 in cardiac fibroblasts inhibited...
Source: Cellular Signalling - July 4, 2020 Category: Cytology Authors: Tao H, Shi P, Zhao XD, Xuan HY, Ding XS Tags: Cell Signal Source Type: research

Janus sword actions of chloroquine and hydroxychloroquine against COVID-19.
Abstract Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have been thrust into our everyday vernacular because some believe, based on very limited basic and clinical data, that they might be helpful in preventing and/or lessening the severity of the pandemic coronavirus disease 2019 (COVID-19). However, lacking is a temperance in enthusiasm for their possible use as well as sufficient perspective on their effects and side-effects. CQ and HCQ have well-known properties of being diprotic weak bases that preferentially accumulate in acidic organelles (endolysosomes and Golgi apparatus) and neutralize lumin...
Source: Cellular Signalling - July 3, 2020 Category: Cytology Authors: Chen X, Geiger JD Tags: Cell Signal Source Type: research

Targeting AMP-activated protein kinase (AMPK) for treatment of autosomal dominant polycystic kidney disease.
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic kidney disease worldwide and an important cause of chronic kidney disease. Multiple experimental studies have highlighted the role of increased mammalian target of rapamycin complex 1 (mTORC1) and reduced AMP-activated protein kinase (AMPK) signaling in modulating cyst growth in ADPKD. Notably, mTORC1 and AMPK are two diametrically opposing sensors of energy metabolism which regulate cell growth and proliferation. Although pharmacological mTORC1 inhibition was highly effective in experimental studies of ADPKD, clinical tri...
Source: Cellular Signalling - July 1, 2020 Category: Cytology Authors: Song X, Tsakiridis E, Steinberg GR, Pei Y Tags: Cell Signal Source Type: research

TNF α-Erk1/2 signaling pathway-regulated SerpinE1 and SerpinB2 are involved in lipopolysaccharide-induced porcine granulosa cell proliferation.
TNFα-Erk1/2 signaling pathway-regulated SerpinE1 and SerpinB2 are involved in lipopolysaccharide-induced porcine granulosa cell proliferation. Cell Signal. 2020 Jun 30;:109702 Authors: Qu X, Guo S, Yan L, Zhu H, Li H, Shi Z Abstract Lipopolysaccharide (LPS) is an inhibitory factor that causes hormonal imbalance and subsequently affects ovarian function and fertility in mammals. Previous studies have shown that the exposure of granulosa cells (GC) to LPS leads to steroidogenesis dysfunction. However, the effects of LPS on the viability of GC remain largely unclear. In the present study, we aimed ...
Source: Cellular Signalling - June 30, 2020 Category: Cytology Authors: Qu X, Guo S, Yan L, Zhu H, Li H, Shi Z Tags: Cell Signal Source Type: research

Targeting chloride transport in autosomal dominant polycystic kidney disease.
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease. Transepithelial fluid secretion is one of the key factors of cystogenesis in ADPKD. Multiple studies have suggested that fluid secretion across ADPKD cyst-lining cells is driven by the secretion of chloride, essentially mediated by the CFTR channel and stimulated by increased intracellular levels of 3',5'-cyclic adenosine monophosphate. This review focuses on the pathophysiology of fluid secretion in ADPKD based on the pioneering studies of Jared Grantham and colleagues, and on the follow-up investigations ...
Source: Cellular Signalling - June 30, 2020 Category: Cytology Authors: Jouret F, Devuyst O Tags: Cell Signal Source Type: research

Circular RNA TUBA1C accelerates the progression of non-small-cell lung cancer by sponging miR-143-3p.
Abstract Non-small-cell lung cancer (NSCLC) is one of the most common solid tumors and the leading cause of lung cancer-related fatality. Growing evidence has indicated that circular RNAs (circRNAs) play important roles in the progression of multiple human cancers. As a novel circRNA, very little research has focused on the function of circRNA TUBA1C (circTUBA1C) in cancer development, including NSCLC. In the present study, we found that the expression of circTUBA1C was significantly upregulated in NSCLC tissues. The loss-of function assays suggested that circTUBA1C deficiency notably hampered cell proliferation a...
Source: Cellular Signalling - June 26, 2020 Category: Cytology Authors: Yang J, Jia Y, Wang B, Yang S, Du K, Luo Y, Li Y, Zhu B Tags: Cell Signal Source Type: research

Signaling pathways that control mRNA translation initiation in macrophages.
Abstract Translational control in mammalian cells plays a critical role in regulating differentiation, cell growth, cell cycle and response to various stresses. Macrophages are one of the most versatile cell types in the body. They are professional phagocytic cells that can be found in almost all tissues and adapt tissue-specific functions. Recent studies highlight the importance of translational control in macrophages during invasion of pathogens, exposure to cytokines and in the context of tissue specific functions. In this review, we summarize the current knowledge regarding the role of mRNA translational contr...
Source: Cellular Signalling - June 25, 2020 Category: Cytology Authors: Tabatabaei N, Hou S, Kim K, Tahmasebi S Tags: Cell Signal Source Type: research

Silence of lncRNA MIAT-mediated inhibition of DLG3 promoter methylation suppresses breast cancer progression via the Hippo signaling pathway.
Abstract As the foremost common female malignancy, breast cancer (BC) poses a significant public health stumbling block. Although treatment protocols have improved over the years, the overall prognosis of BC remains unsatisfactory. Extensive investigations have taken place into long non coding RNAs (lncRNAs) pertaining to their involvement in carcinogenesis. The current study in connection with bioinformatics tools aimed to identify the myocardial infarction associated transcript (MIAT) as a BC-related differentially expressed lncRNA in an attempt to elucidate the effect of MIAT in BC cells. MIAT was initially ove...
Source: Cellular Signalling - June 25, 2020 Category: Cytology Authors: Li D, Hu X, Yu S, Deng S, Yan M, Sun F, Song J, Tang L Tags: Cell Signal Source Type: research

Unfolded protein response in cardiovascular disease.
Abstract The unfolded protein response (UPR) is a highly conserved molecular machinery, which protects the cells against a diverse variety of stimuli. Activation of this element has been associated with both human health and disease. The purpose of the current manuscript is to provide the most updated information on the corresponding field, and to shed light on the involvement of UPR towards the improvement; or deterioration of cardiovascular functions. Since UPR is consisted of three distinct elements, namely the activating transcription factor 6, the protein kinase RNA-like ER kinase; and the inositol-requiring ...
Source: Cellular Signalling - June 24, 2020 Category: Cytology Authors: Kubra KT, Akhter MS, Uddin MA, Barabutis N Tags: Cell Signal Source Type: research

Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease.
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases implicated in the development of end stage renal disease (ESRD). Although FDA has recently approved a drug against ADPKD, there is still a great need for development of alternative management strategies for ADPKD. Understanding the different mechanisms that lead to cystogenesis and cyst expansion in ADPKD is imperative to develop new therapies against ADPKD. Recently, we demonstrated that caloric restriction can prevent the development of cystic disease in animal models of ADPKD and through these studies identi...
Source: Cellular Signalling - June 19, 2020 Category: Cytology Authors: Kashyap S, Zeidler JD, Chini CCS, Chini EN Tags: Cell Signal Source Type: research

LncRNA CALB2 sponges miR-30b-3p to promote odontoblast differentiation of human dental pulp stem cells via up-regulating RUNX2.
Abstract Illuminating the mechanisms of odontoblast differentiation of human dental pulp stem cells (hDPSCs) is the key to find therapeutic clues to promote odontogenesis. LncRNAs play a regulatory role in odontoblast differentiation. Here, we identified a novel lncRNA, named lncRNA CALB2. It was up-regulated in odontoblast-differentiated hDPSCs and potentially interacted with miR-30b-3p and RUNX2. Via gain- and loss-of-function approaches, we found lncRNA CALB2 significantly promoted the odontoblast differentiation of hDPSCs. Then, dual luciferase reporter assay and RNA immunoprecipitation assay revealed that bot...
Source: Cellular Signalling - June 18, 2020 Category: Cytology Authors: Tu S, Wu J, Chen L, Tian Y, Qin W, Huang S, Wang R, Lin Z, Song Z Tags: Cell Signal Source Type: research

Minocycline reverses IL-17A/TRAF3IP2-mediated p38 MAPK/NF- κB/iNOS/NO-dependent cardiomyocyte contractile depression and death.
Minocycline reverses IL-17A/TRAF3IP2-mediated p38 MAPK/NF-κB/iNOS/NO-dependent cardiomyocyte contractile depression and death. Cell Signal. 2020 Jun 15;:109690 Authors: Yoshida T, Das NA, Carpenter AJ, Izadpanah R, Kumar SA, Gautam S, Bender SB, Siebenlist U, Chandrasekar B Abstract Minocycline, an FDA-approved second-generation semisynthetic tetracycline, exerts antioxidant, anti-apoptotic and anti-inflammatory effects, independent of its antimicrobial properties. Interleukin (IL)-17A is an immune and inflammatory mediator, and its sustained induction is associated with various cardiovascular d...
Source: Cellular Signalling - June 15, 2020 Category: Cytology Authors: Yoshida T, Das NA, Carpenter AJ, Izadpanah R, Kumar SA, Gautam S, Bender SB, Siebenlist U, Chandrasekar B Tags: Cell Signal Source Type: research

Characteristics of circular RNAs generated by human Survival Motor Neuron genes.
Abstract Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA structures formed by an exceptionally high number of Alu repeats lead to the production of a vast repertoire of circRNAs by human Survival Motor Neuron genes, SMN1 and SMN2, that code for SMN, an essential multifunctional protein. Low levels of SMN due to deletion or mutation of SMN1 result in...
Source: Cellular Signalling - June 15, 2020 Category: Cytology Authors: Ottesen EW, Singh RN Tags: Cell Signal Source Type: research

CTRP9: An emerging potential anti-aging molecule in brain.
Abstract C1q/tumor necrosis factor (TNF)-related proteins (CTRPs) particularly CTRP9, have been established to be as adiponectin (APN) highly conserved paralogs which assemble several APN regulatory functions. Recently, growing body of evidences drawn significant attention to evaluate metabolic and cardiovascular effect of CTRP9. However, the potential role of CTRP9 in brain tissue has not yet fully illustrated. Here, we aimed to uncover latest advances regarding the CTRP9 related signaling pathways and during brain aging process. PMID: 32540339 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - June 12, 2020 Category: Cytology Authors: Rezabakhsh A, Sadeghipour Y, Ghaderi S, Rahbarghazi R, Geranmaye MH Tags: Cell Signal Source Type: research

Phosphorylation of the mRNA cap-binding protein eIF4E and cancer.
Abstract Dysregulated protein synthesis is frequently involved in oncogenesis and cancer progression. Translation initiation is thought to be the rate-limiting step in protein synthesis, and the mRNA 5' cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) is a pivotal factor that initiates translation. The activities of eIF4E are regulated at multiple levels, one of which is through its phosphorylation at Serine 209 by the mitogen-activated protein kinase-interacting kinases (MNKs, including MNK1 and MNK2). Benefiting from novel mouse genetic tools and pharmacological MNK inhibitors, our underst...
Source: Cellular Signalling - June 11, 2020 Category: Cytology Authors: Yang X, Zhong W, Cao R Tags: Cell Signal Source Type: research

IRSp53 is a novel interactor of SHIP2: A role of the actin binding protein Mena in their cellular localization in breast cancer cells.
We presented evidence that IRSp53 phosphorylation on S366 did not influence its interaction with SHIP2 and that Mena is not necessary for the association of SHIP2 with IRSp53 in MDA-MB-231 cells. The absence of Mena in MDA-MB-231 cells decreased the intracellular content in F-actin and modified the subcellular localization of SHIP2 and IRSp53 by increasing their relative content at the plasma membrane. Together our data suggest that SHIP2, through interaction with the cell protrusion regulators IRSp53 and Mena, participate to the formation of multi-protein complexes. This ensures the appropriate modulations of PIs which is...
Source: Cellular Signalling - June 11, 2020 Category: Cytology Authors: Antoine M, Vandenbroere I, Ghosh S, Erneux C, Pirson I Tags: Cell Signal Source Type: research

MAP Kinase driven actomyosin rearrangement is a crucial regulator of monocyte to macrophage differentiation.
Abstract Rearrangement of actin cytoskeleton correlates significantly with the immune responses as the perturbation of cytoskeletal dynamics leads to many immune deficiencies. Mechanistic insights into this correlation remain unknown. Cellular spreading, the most characteristic phenotype associated with monocyte to macrophage differentiation, led us to investigate the contribution of actomyosin dynamics in monocyte differentiation. Our observation revealed that actomyosin reorganization intrinsically governs the process of monocyte to macrophage differentiation. Further, we established that the MAPK-driven signali...
Source: Cellular Signalling - June 9, 2020 Category: Cytology Authors: Bhattacharya A, Ghosh P, Prasad R, Ghosh A, Das K, Roy A, Mallik S, Sinha DK, Sen P Tags: Cell Signal Source Type: research

The NF- κB signalling pathway regulates GLUT6 expression in endometrial cancer.
CONCLUSIONS: TNFα is a cytokine that is commonly increased in obesity-related endometrial cancer and the findings herein support a potential mechanism whereby TNFα may contribute to endometrial cancer initiation or progression by increasing GLUT6 expression. Furthermore, we identified RELA, an important downstream mediator of the TNFα signalling cascade, as a regulator of GLUT6 expression in endometrial cells. Future studies are warranted to determine how GLUT6 expression affects endometrial tumourigenesis or cancer progression. PMID: 32512041 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - June 5, 2020 Category: Cytology Authors: Caruana BT, Byrne FL Tags: Cell Signal Source Type: research

SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway.
Abstract In cancers, apoptosis evasion through dysregulation of pro-apoptotic and anti-apoptotic intracellular signals is a recurring event. Accordingly, selective inhibition of specific proteins represents an exciting therapeutic opportunity. Myeloid cell leukemia 1 (MCL1) is an anti-apoptotic protein of the BCL-2 family, which is overexpressed in many cancers. Here, we demonstrate that MCL1 can be modified by the small ubiquitin-like modifier (SUMO) at K234 and K238 sites. The SUMOylation of MCL1 can improve its stability by inhibiting the MCL1 ubiquitin-proteasome pathway mediated by the Tripartite motif-contai...
Source: Cellular Signalling - June 3, 2020 Category: Cytology Authors: Li S, Wang J, Hu G, Aman S, Li B, Li Y, Xia K, Yang Y, Ahmad B, Wang M, Wu H Tags: Cell Signal Source Type: research