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Now showing items 3921-3940 of 4628
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Structural transitions in the GTP cap visualized by cryo-electron microscopy of catalytically inactive microtubules.
(NATL ACAD SCIENCES, 2022-01-11)Microtubules (MTs) are polymers of αβ-tubulin heterodimers that stochastically switch between growth and shrinkage phases. This dynamic instability is critically important for MT function. It is believed that GTP hydrolysis ... -
Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.
(OXFORD UNIV PRESS INC, 2022-06-01)We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an ... -
The structure and mechanism of the EXD2 nuclease in DNA repair
(Institute of Cancer Research (University Of London), 2023-06-09)DNA double strand breaks (DSBs) are one of the most toxic DNA lesions. They can jeopardise stability of the genome and lead to cancer development. There are two main pathways of DSB repair: homologous recombination (HR) ... -
Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
(AMER CHEMICAL SOC, 2015-03-12)The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 ... -
Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling.
(NATURE PORTFOLIO, 2022-08-29)Genes encoding the core cell cycle machinery are transcriptionally regulated by the MuvB family of protein complexes in a cell cycle-specific manner. Complexes of MuvB with the transcription factors B-MYB and FOXM1 activate ... -
Structure of human RNA polymerase III.
(NATURE RESEARCH, 2020-12-17)In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III ... -
Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction.
(OXFORD UNIV PRESS, 2022-08-12)The RAD9-RAD1-HUS1 (9-1-1) clamp forms one half of the DNA damage checkpoint system that signals the presence of substantial regions of single-stranded DNA arising from replication fork collapse or resection of DNA double ... -
Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
(2001-04-24)The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA, These ... -
Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds.
(NATL ACAD SCIENCES, 2019-02-12)The RAS gene family is frequently mutated in human cancers, and the quest for compounds that bind to mutant RAS remains a major goal, as it also does for inhibitors of protein-protein interactions. We have refined ... -
Structure-based drug design: aiming for a perfect fit.
(PORTLAND PRESS LTD, 2017-11-08)Knowledge of the three-dimensional structure of therapeutically relevant targets has informed drug discovery since the first protein structures were determined using X-ray crystallography in the 1950s and 1960s. In this ... -
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
(AMER CHEMICAL SOC, 2016-10-27)The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ... -
Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1.
(WILEY-V C H VERLAG GMBH, 2017-07-18)TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein-protein interaction represents a putative cancer target, but no ... -
Structure-guided design of purine-based probes for selective Nek2 inhibition
(2017)Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can ... -
Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor.
(NATURE PUBLISHING GROUP, 2011-02-10)The ubiquitylation of cell-cycle regulatory proteins by the large multimeric anaphase-promoting complex (APC/C) controls sister chromatid segregation and the exit from mitosis. Selection of APC/C targets is achieved through ... -
Study of Plasmodium falciparum DHHC palmitoyl transferases identifies a role for PfDHHC9 in gametocytogenesis.
(WILEY, 2016-11-01)Palmitoylation is the post-translational reversible addition of the acyl moiety, palmitate, to cysteine residues of proteins and is involved in regulating protein trafficking, localization, stability and function. The ... -
Study protocol for a randomised controlled trial of enhanced informed consent compared to standard informed consent to improve patient understanding of early phase oncology clinical trials (CONSENT).
(BMJ PUBLISHING GROUP, 2021-09-06)INTRODUCTION: Early phase cancer clinical trials have become increasingly complicated in terms of patient selection and trial procedures-this is reflected in the increasing length of participant information sheets (PIS). ... -
Study within a trial of electronic versus paper-based Patient-Reported oUtcomes CollEction (SPRUCE): study protocol for a partially randomised patient preference study.
(BMJ PUBLISHING GROUP, 2023-09-21)INTRODUCTION: Patient-reported outcomes (PRO) are currently collected from trial participants using paper questionnaires by the Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU). Streamlining ... -
Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation.
(CELL PRESS, 2017-11-14)The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their ... -
Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an 'Immune Cold' Phenotype Associated with Poor Survival.
(MDPI, 2023-03-20)New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant ... -
Subcellular protein expression models for microsatellite instability in colorectal adenocarcinoma tissue images
(2016-10-01)Background: New bioimaging techniques capable of visualising the co-location of numerous proteins within individual cells have been proposed to study tumour heterogeneity of neighbouring cells within the same tissue specimen. ...