A5013884482- RNA modifications and cancer
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- RNA regulation and disease
- Genital Health and Disease
- MicroRNA in disease regulation
- interferon and immune responses
- Viral-associated cancers and disorders
- Congenital Diaphragmatic Hernia Studies
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Tissue Engineering and Regenerative Medicine
- RNA and protein synthesis mechanisms
- Mechanisms of cancer metastasis
- Genetic factors in colorectal cancer
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
- Virus-based gene therapy research
- Law, AI, and Intellectual Property
- Histiocytic Disorders and Treatments
- Extracellular vesicles in disease
- Cancer-related Molecular Pathways
Queen Mary University of London
2014-2025
Cancer Institute (WIA)
2024-2025
Cancer Research UK
2000-2023
Institute of Cancer Research
2020
University of Nottingham
2008-2013
Queen's Medical Centre
2008-2013
University College London
2000-2004
Karolinska Institutet
2004
Royal Brompton Hospital
2004
Hologic (Germany)
2002
ABSTRACT The Kaposi’s sarcoma-associated herpesvirus (KSHV) (or human 8) open reading frame (ORF) K15 encodes a putative integral transmembrane protein in the same genomic location as latent membrane 2A of Epstein-Barr virus. Ectopic expression cell lines revealed presence several different forms ranging size from full length, ∼50 kDa, to 17 kDa. Of these species 35- and 23-kDa were predominant. Mutational analysis initiator AUG indicated that translation initiation this first is required...
The interferon-inducible protein kinase PKR interacts with a number of small viral RNA species, including adenovirus VA, and the Epstein-Barr virusencoded EBER-1. These RNAs bind to protect synthesis from inhibition by doublestranded in reticulocyte lysate system. Using peptide phosphorylation assay we show here that EBER-1, like VA,, directly inhibits activation purified PKR. A second virus RNA, EBER-2, also regulates EBER-2 exhibit mutually competitive binding native or recombinant enzyme,...
Planarian flatworms are able to both regenerate their whole bodies and continuously adapt size nutrient status. Tight control of stem cell proliferation differentiation during these processes is the key feature planarian biology. Here we show that homolog phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 mTOR complex 1 components required for this tight control. Loss smg-1 results in a hyper-responsiveness injury growth formation regenerative blastemas remain...
Abstract Other than an association with HPV infection, little is known about the genetic alterations determining development of penile cancer. Although cancer rare in developed world, it presents a significant burden developing countries. Here, we report findings whole-exome sequencing (WES) to determine somatic mutational landscape WES was performed on and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing candidate genes independent 70 patient...
Highlights•LIMD1 is necessary for the Akt3-dependent assembly of an AGO-TNRC6A functional miRISC•AGO1, 2, and 4 recruit LIMD1 in a phospho-dependent manner•AGO2 to AGO3 switching occurs upon ablation HeLa cells•AGO3-WTIP replaces AGO2-LIMD1 miRNA silencing Akt3-independent mannerSummaryAs core components microRNA-induced complex (miRISC), Argonaute (AGO) proteins interact with TNRC6 proteins, recruiting other effectors translational repression/mRNA destabilization. Here, we show that...
LIM domains-containing protein 1 (LIMD1) is encoded at chromosome 3p21.3, a region commonly deleted in many solid malignancies. However, the function of LIMD1 unknown. Here we show that specifically interacts with retinoblastoma (pRB), inhibits E2F-mediated transcription, and suppresses expression majority genes E2F1-responsive elements. blocks tumor growth vitro vivo down-regulated human lung cancer samples tested. Our data indicate tumor-suppressor gene, product which functionally pRB loss...
ABSTRACT Kaposi's sarcoma (KS) associated herpesvirus (KSHV) is the etiological agent of KS. In vivo, KS a tumor capable spreading throughout body, and pulmonary metastasis observed clinically. vitro, KSHV induces invasiveness endothelial cells. The open reading frame K15 KSHV-specific gene encoding transmembrane protein. Two highly divergent forms K15, predominant (P) minor (M) (K15P K15M, respectively), have been identified in different strains. two alleles resemble latent membrane protein...
In recent years there have been major advances with respect to the identification of protein components and mechanisms microRNA (miRNA) mediated silencing. However, complete precise repertoire mechanism(s) action remain be fully elucidated. Herein we reveal a family three LIM domain-containing proteins, LIMD1, Ajuba WTIP (Ajuba proteins) as novel mammalian processing body (P-body) components, which highlight mechanism miRNA-mediated gene Furthermore, that Ajuba, bind Ago1/2, RCK, Dcp2, eIF4E...
Loss of heterozygosity (LOH) and homozygous deletions at chromosome 3p21.3 are common in both small nonsmall cell lung cancers, indicating the likely presence tumor suppressor genes (TSGs). Although genetic epigenetic changes within this region have been identified, functional significance these has not explored. Concurrent protein expression analyses human tumors coupled with studies done. Here, we show that gene, LIMD1, is frequently down-regulated tumors. LIMD1 occurs through a...
Air-liquid interface (ALI) culture of primary airway epithelial cells enables mucociliary differentiation providing an in vitro model the human airway, but their proliferative potential is limited. To extend proliferation, these were previously transduced with viral oncogenes or mouse Bmi-1 + hTERT, resultant cell lines did not undergo differentiation. We hypothesized that use BMI-1 alone would increase bronchial while retaining potential. Cystic fibrosis (CF) and non-CF by lentivirus then...
LIMD1 is a tumour suppressor gene frequently lost in non-small cell lung cancer (NSCLC), but its role cancer-immune interactions remains unexplored. Here, we demonstrate that loss results upregulation of the key immune checkpoint protein PD-L1. Using multi-region sequencing from TRACERx dataset, identify clonal over 80% squamous carcinoma (LUSC) and 40% adenocarcinoma (LUAD) cases, correlating with increased PD-L1 expression. deficiency basal IFNγ-induced expression NSCLC cells and,...
<title>Abstract</title> LIMD1 is a tumour suppressor gene frequently lost in non-small cell lung cancer (NSCLC), but its role cancer-immune interactions remains unexplored. Here, we demonstrate that loss results upregulation of the key immune checkpoint protein PD-L1. Using multi-region sequencing from TRACERx dataset, identify clonal over 80% squamous carcinoma (LUSC) and 40% adenocarcinoma (LUAD) cases, correlating with increased PD-L1 expression. deficiency basal IFNγ-induced expression...
The La (SS-B) autoimmune antigen is an RNA-binding protein that present in both nucleus and cytoplasm of eukaryotic cells. spectrum RNAs interact with the includes species which also bind to interferon-inducible kinase PKR. We have investigated whether can regulate activity PKR observed autophosphorylation accompanies its activation by dsRNA dsRNA-dependent phosphorylation alpha subunit polypeptide chain initiation factor eIF-2 are inhibited presence recombinant antigen. This inhibition...
The vaccinia virus K3L gene product, pK3, binds to the dsRNA‐activated protein kanase, PKR, reducing its ability interact with and phosphorylate eIF2α. On basis of this characteristic homology pK3 N‐terminus eIF2α, several laboratories have utilized investigate molecular determinants that specify substrate recognition by PKR. data presented here demonstrate natural substrate, also PKR in vitro interacts same or an overlapping domain within A truncated form representing N‐terminal 123 amino...
Compounds targeting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling are being investigated in multiple clinical settings, but drug resistance may reduce their benefit. Compound rechallenge after holidays can overcome such resistance, yet little is known about the impact on cell biochemistry. We found that PI3K inhibitor (PI3Ki)-resistant cells cultured absence PI3Ki developed a proliferative defect, increased oxygen consumption and accumulated reactive...
The abundance of miR-132 ranges from constitutively high in the brain where it is necessary for neuronal development and function, to inducible expression haematopoietic endothelial cells controls angiogenesis immune activation. We show that AGO2, a protein central miRNA-mediated gene silencing miRNA biogenesis, negatively regulated by miR-132. Using HeLa cells, we demonstrate interacts with AGO2 mRNA 3'UTR suppresses AGO2-dependent small RNA-mediated silencing. Similarly, over-expression...
The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action poorly characterised. Our aims were identify ajmaline's human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform test whether differences response could be determined between patients controls. Control hiPSCs differentiated into spontaneously contracting cardiac clusters. It was...
Research Article21 June 2018Open Access Source DataTransparent process A HIF–LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia Daniel E Foxler orcid.org/0000-0003-3753-0278 Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University London, UK Search more papers by this author Katherine S Bridge orcid.org/0000-0003-1516-1459 John G Foster orcid.org/0000-0002-8591-0833 Paul Grevitt orcid.org/0000-0001-8224-1315 Sean Curry Faculty Medicine and...