A5056280779- RNA Research and Splicing
- Protease and Inhibitor Mechanisms
- Ion Channels and Receptors
- Nuclear Structure and Function
- MicroRNA in disease regulation
- Protein Kinase Regulation and GTPase Signaling
- RNA and protein synthesis mechanisms
- Cellular Mechanics and Interactions
- Phytochemicals and Antioxidant Activities
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Brucella: diagnosis, epidemiology, treatment
- Legionella and Acanthamoeba research
- Circular RNAs in diseases
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Hepatitis C virus research
- Extracellular vesicles in disease
- Ubiquitin and proteasome pathways
- Intracranial Aneurysms: Treatment and Complications
- Leptospirosis research and findings
- Cancer Cells and Metastasis
- Muscle Physiology and Disorders
- Burkholderia infections and melioidosis
St George's, University of London
2014-2024
City St George's, University of London
2024
The Francis Crick Institute
2007-2016
The Honourable Society of Lincoln's Inn
2003-2016
University of London
2015
St George’s University Hospitals NHS Foundation Trust
2007
Cancer Research UK
2003-2006
Stockholm University
2000-2003
Universitat de Barcelona
1996-2000
Institut Català d'Oncologia
1999
Myocardin (MC) family proteins are transcriptional coactivators for serum response factor (SRF). Each member possesses a conserved N-terminal region containing three RPEL motifs (the "RPEL domain"). MAL/MKL1/myocardin-related transcription A is cytoplasmic, accumulating in the nucleus upon activation of Rho GTPase signaling, which alters interactions between G-actin and domain. We demonstrate that MC, nuclear, does not shuttle through cytoplasm contrasting nucleocytoplasmic shuttling...
Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of transcriptional activation domain (TAD) Elk-1 by protein kinase ERK at multiple sites potentiates recruitment Mediator coactivator complex and activation, but roles individual events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 proceeds markedly different rates eight TAD in vitro, which classified as...
To determine the function of actin in cell nucleus, we sought to identify nuclear actin-binding proteins dipteran Chironomus tentans using DNase I-affinity chromatography. We identified RNA-binding protein hrp65 as an and showed that C-terminal sequence hrp65-2 isoform is able interact directly with vitro. In vivo crosslinking coimmunoprecipitation experiments indicated are also associated living cell. Moreover, administration a competing peptide corresponding disrupted actin–hrp65-2...
Ion channels play pivotal roles in regulating important functions of macrophages, such as cytokine and chemokine production, migration, proliferation, phagocytosis others. In this study, we have identified a novel ion channel type namely transient receptor potential M7 (TRPM7) channels. TRPM7 activity is differentially regulated i.e. current density significantly larger anti-inflammatory M2-type macrophages than untreated pro-inflammatory M1-type while mRNA levels remain unchanged upon cell...
The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner factor SRF. MRTFs bind G-actin, signal-regulated changes in cellular G-actin concentration control nuclear accumulation. also undergo Rho- ERK-dependent phosphorylation, but the function of MRTF elements signals involved MRTF-A export are largely unexplored. We show that Rho-dependent phosphorylation reflects relief from an inhibitory actin. map multiple sites serum-induced most...
Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes tumors and according genomic, transcriptomic, proteomic alterations. This study underlines role microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cells. Following knockout miR-21 from cells, which highest expression levels compared MCF-7 SK-BR-3 BCa a decrease...
ABSTRACT In order to evaluate the diagnostic yield of a PCR assay for patients with focal complications brucellosis, we studied by and conventional microbiological techniques 34 nonblood samples from 32 different forms brucellosis. The brucellosis were paired an equal number control same locations whose illnesses had etiologies. Thirty-three (97%) positive PCR, whereas Brucella spp. isolated only 29.4% cultures. For 11.4% patients, confirmatory serological tests either negative or showed...
The transcription factor serum response (SRF) interacts with its cofactor, MAL/MKL1, a member of the myocardin-related (MRTF) family, through DNA-binding domain. We define seven-residue sequence within conserved MAL B1 region essential and sufficient for complex formation. neighboring Q-box facilitates this interaction. regions also have antagonistic effects on nuclear import, but residues involved are largely distinct. Both ternary (TCF) family SRF cofactors interact hydrophobic groove...
Article20 December 2017Open Access Source DataTransparent process WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome Yeon-Joo Kim orcid.org/0000-0001-8896-1153 Molecular and Clinical Sciences Research Institute, St. George's, University of London, UK Search for more papers by this author Daniel PS Osborn Ji-Young Lee Masatake Araki Institute Resource Development Analysis, Kumamoto University, Kumamoto, Japan Kimi Timothy Mohun Francis Crick...
Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer (PCa) with a low survival rate. microRNAs (miRs) are endogenous, non-coding RNAs that moderate numerous biological processes. miRs have been associated chemoresistance metastasis PDAC presence subpopulation highly plastic "stem"-like cells within tumor, known as stem (CSCs). In this study, we investigated role miR-21, which expressed in Panc-1 MiaPaCa-2 association CSCs. Following miR-21...
Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage are hallmarks of brain aging, traumatic injury neurodegenerative diseases. It is, thus, particular interest identify mechanisms involved in microglial priming. Here, we demonstrate that microglia with interferon-γ (IFN γ) substantially production reactive oxygen species (ROS) following stimulation ATP. Priming ROS was reduced by inhibition p38 MAPK activity SB203580, increases intracellular...
Key points Depletion of Ca 2+ stores activates store‐operated channels (SOCs), which mediate entry pathways that regulate cellular processes such as contraction, proliferation and gene expression. In vascular smooth muscle cells (VSMCs), stimulation SOCs composed canonical transient receptor potential channel 1 (TRPC1) proteins requires G protein α q subunit (Gαq)/phospholipase C (PLC)β1/protein kinase (PKC) activity. We studied the role stromal interaction molecule (STIM1) in coupling store...
Using electron tomography, we have analyzed whether the Balbiani ring (BR) pre-mRNP particles in transit from gene to nuclear pore complex (NPC) are bound any structure that could impair free diffusion through nucleoplasm. We show one-third of BR contact with thin connecting fibers (CFs), which some cases merge into large fibrogranular clusters. The CFs a specific protein composition different particles, as shown by immuno-EM. Moreover, identified hrp65 one components CFs. sequencing cDNA...
ABSTRACTABSTRACTUV irradiation leads to severe damage, such as cutaneous inflammation, immunosuppression, and cancer, but it also results in a gene induction protective response termed the UV response. The signal triggering was thought originate from DNA damage; recent findings, however, have shown that is initiated at or near cell membrane transmitted via cytoplasmic kinase cascades induce transcription. Urokinase-type plasminogen activator (uPA) first protein be inducible xeroderma...
Depletion of sarcoplasmic reticulum (SR) Ca2+ stores activates store-operated channels (SOCs) composed canonical transient receptor potential (TRPC) 1 proteins in vascular smooth muscle cells (VSMCs), which contribute to important cellular functions. We have previously shown that PKC is obligatory for activation TRPC1 SOCs VSMCs, and the present study investigates if classic phosphoinositol signaling pathway involving Gαq-mediated PLC activity responsible driving PKC-dependent channel...
Mechanistic target of rapamycin (mTOR) is a fundamental regulator cell growth, proliferation, and metabolism. mTOR activated in renal cancer accelerates tumor progression. Here, we report that the inhibitor, DEP domain-containing mTOR-interacting protein (DEPTOR), strikingly suppressed clear carcinoma (ccRCC) tumors lines. We demonstrate DEPTOR repressed by both hypoxia-inducible factors, HIF-1 HIF-2, which occurs through activation HIF-target gene transcriptional repressor,...
Ca2+-permeable store-operated channels (SOCs) mediate Ca2+ entry pathways which are involved in many cellular functions such as contraction, growth, and proliferation. Prototypical SOCs formed of Orai1 proteins activated by the endo/sarcoplasmic reticulum sensor stromal interaction molecule 1 (STIM1). There is considerable debate about whether canonical transient receptor potential (TRPC1) also form (SOCs), if they do, involved. We recently showed that stimulation TRPC1-based involves store...
Pancreatic ductal adenocarcinoma (PDAC) is one among the most lethal malignancies due to its aggressive behavior and resistance conventional therapies. Hypoxia significantly contributes cancer progression therapeutic of PDAC. microRNAs (miRNAs/miRs) have emerged as critical regulators various biological processes. miR-210 known "hypoxamir" prominent role in cellular responses hypoxia. In this study, we investigated multifaceted PDAC using knockout (KO) models elucidate functions under...
Summary Urokinase-type plasminogen activator (uPA) is one of the components blood’s fibrinolytic cascade. uPA acts as a broad spectrum proteolytic enzyme involved in different physio-pathological processes including cellular fibrinolysis, adhesion, migration, invasion and remodeling. Here, we present evidence that participates myogenesis, process which requires drastic cell membrane reorganization, leading to plurinucleated myotube from progenitor myoblast. We have dissected expression...