Results 81 to 90 of about 67,942 (278)

Heterozygous loss‐of‐function alleles associate the conserved 3′‐5′ exoribonuclease EXOSC10 with hypersensitivity to the anticancer drug 5‐fluorouracil

Molecular Oncology, EarlyView.
EXOSC10, an essential nuclear RNA exosome‐associated 3′‐5′ exoribonuclease, is inhibited by the anticancer drug 5‐fluorouracil (5‐FU), and EXOSC10 depletion increases 5‐FU sensitivity. The colon‐cancer variant EXOSC10S402T, located in a proteolysis motif, is stable and nuclear but nonfunctional in vivo.
Radhika Sain, Yann Le Page, Frédéric Percevault, Emmanuelle Becker, Luc Negroni, Almudena Fernandez, Marta Cantero, Diego Muñoz‐Santos, Lluís Montoliu, Cyrille Garnier, Michael Primig   +10 more
wiley   +1 more source

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

Molecular Oncology, EarlyView.
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder, Klaas de Lint, Hồ Mỹ Phúc Võ, Mariana M. Góis, Rosalie A. Kampen, Marta San Martin Alonso, Ilse Nootenboom, Veronica Garzero, Tiemen J. Wendel, Rob M. F. Wolthuis, Sylvie M. Noordermeer   +10 more
wiley   +1 more source

Neutrophil Elastase Mediates Pathogenic Effects of Anthrax Lethal Toxin in the Murine Intestinal Tract

, 2010
Neutrophils isolated from BALB/c or C57BL/6 mice and treated in vitro with anthrax lethal toxin release bioactive neutrophil elastase, a proinflammatory mediator of tissue destruction. Similarly, neutrophils isolated from mice treated with anthrax lethal
Roger D. Auth, David M. Frucht, Chen Sun, Hui Fang, Robert J. Owen, Lixin Xu, Philip J. Snoy   +6 more
core   +1 more source

Clostridium sordellii Lethal-Toxin Autoprocessing and Membrane Localization Activities Drive GTPase Glucosylation Profiles in Endothelial Cells

mSphere, 2016
Clostridium sordellii infections cause gangrene and edema in humans and gastrointestinal infections in livestock. One of the principle virulence factors is TcsL, a large protein toxin which glucosylates host GTPases to cause cytopathic and cytotoxic ...
Ryan Craven, D. Borden Lacy
doaj   +1 more source

Effects of anthrax lethal toxin on human primary keratinocytes [PDF]

Journal of Applied Microbiology, 2008
To investigate the effects of anthrax lethal toxin (LeTx) on human primary keratinocytes.We show here that human primary keratinocytes are resistant to LeTx-triggered cytotoxicity. All but one of the MEKs (mitogen-activated protein kinase kinases) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome ...
S S, Koçer, M, Matic, M, Ingrassia, S G, Walker, E, Roemer, G, Licul, S R, Simon   +6 more
openaire   +2 more sources

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

Molecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington, Divya L. Dayanidhi, Mohammad Zokaasadi, John B. Mantyh, Pelumi D. Olawuni, Gabrielle Rupprecht, Jeremy M. Force, Shannon McCall, Ashwani K. Bahl, David S. Hsu, Jason A. Somarelli   +10 more
wiley   +1 more source

Protection of TcdA rRBD against lethal toxin A challenge.

, 2015
(A) BALB/c mice were challenged with a lethal dose of toxin A two weeks after three immunizations with TcdA rRBD (0.3, 3, and 30 μg) via intramuscular injection.
Pele Choi-Sing Chong (314717), Chi-Chang Chen (783029), Leung-Kei Siu (407937), Jui-Hsin Huang (783026), Zhe-Qing Shen (783027), Shu-Pei Lien (783028), Chih-Hsiang Leng (315469), Kuang-Nan Hsiao (296109)   +7 more
core   +1 more source

Aquaporin‐3 and aquaporin‐5 impact the development of pancreatic ductal adenocarcinoma spheroids

FEBS Open Bio, EarlyView.
Schematic representation of the role of aquaporin‐3 (AQP3) and aquaporin‐5 (AQP5) in pancreatic ductal adenocarcinoma (PDAC). Both proteins are upregulated in PDAC and are associated with tumor progression and metastatic potential. Silencing AQP3 or AQP5 in PDAC spheroids results in decreased diameter, area, and overall growth, underscoring their key ...
Catarina Pimpão, Diogo M. Engrácia, Graça Soveral, Filipa Mendes   +3 more
wiley   +1 more source

Molecular characterization of covRS mutations in M1UK Streptococcus pyogenes

FEBS Open Bio, EarlyView.
Group A Streptococcus (GAS) acquires covRS mutations driving a hypervirulent bacterial state, frequently associated with invasive disease‐like necrotizing fasciitis. We demonstrate that the newly emerged M1UK GAS lineage can also acquire these mutations.
Jarrad Pritchard, Emma‐Jayne Proctor, Jiawa Wang, Nikolas P. Johnston, Andrew Hayes, Georgia McCorkell, Haibo Yu, Jai Tree, Mark R. Davies, Mark J. Walker, Ronald Sluyter, Stephan Brouwer, Martina L. Sanderson‐Smith   +12 more
wiley   +1 more source

The isolation and characterisation of temperature-dependent Ricin A chain molecules in Saccharomyces cerevisiae. [PDF]

, 2007
Ricin is a heterodimeric plant protein that is potently toxic to mammalian cells. Toxicity results from the catalytic depurination of eukaryotic ribosomes by ricin A chain (RTA) that follows toxin endocytosis to, and translocation across, the ...
Ladds, Graham, Moffat, K G, Allen, Stuart C H, Fulop, V, Moore, Katherine A. H., Marsden, Catherine J., Marsden, C J, Ladds, G, Roberts, L M, Lord, Mike, Lord, J M, Allen, Stuart C. H., Roberts, L. M. (Lynne M.), Moffat, Kevin G., Fülöp, Vilmos, Moore, K A H   +15 more
core   +1 more source