Results 91 to 100 of about 5,065,932 (329)

Mechanistic basis for inhibition of the extended‐spectrum β‐lactamase GES‐1 by enmetazobactam and tazobactam

open access: yesFEBS Letters, EarlyView.
Antimicrobial resistance (AMR) is of huge importance, resulting in over 1 million deaths each year. Here, we describe how a new drug, enmetazobactam, designed to help fight resistant bacterial diseases, inhibits a key enzyme (GES‐1) responsible for AMR. Our data show it is a more potent inhibitor than the related tazobactam, with high‐level computation
Michael Beer   +10 more
wiley   +1 more source

C9orf72 ALS‐causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules

open access: yesFEBS Letters, EarlyView.
Mutations in the C9orf72 gene represent the most common genetic cause of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Using patient‐derived neurons and C. elegans models, we find that the nucleoporin Nup107 is dysregulated in C9orf72‐associated ALS. Conversely, reducing Nup107 levels mitigates disease‐related changes.
Saygın Bilican   +7 more
wiley   +1 more source

From lactation to malignancy: A comparison between healthy and cancerous breast gland at single‐cell resolution reveals new issues for tumorigenesis

open access: yesFEBS Letters, EarlyView.
Single‐cell RNA sequencing reveals an opposite role of SLPI in basal tumors based on metastatic spread, along with shared activation of specific regulons in cancer cells and mature luminal lactocytes, as well as downregulation of MALAT1 and NEAT1 in the latter.
Pietro Ancona   +4 more
wiley   +1 more source

Imeglimin attenuates liver fibrosis by inhibiting vesicular ATP release from hepatic stellate cells

open access: yesFEBS Letters, EarlyView.
Imeglimin, at clinically relevant concentrations, inhibits vesicular ATP accumulation and release from hepatic stellate cells, thereby attenuating purinergic signaling and reducing fibrogenic activation. This mechanism reveals a newly identified antifibrotic action of imeglimin beyond glycemic control.
Seiji Nomura   +8 more
wiley   +1 more source

Cancer cell death induced by the NAD antimetabolite Vacor discloses the antitumor potential of SARM1

open access: yesFEBS Letters, EarlyView.
Vacor, a compound converted into the toxic metabolite Vacor adenine dinucleotide (VAD) by the nicotinamide salvage pathway enzymes NAMPT and NMNAT2, exhibits antitumor activity by inducing rapid and complete NAD depletion. We report that Vacor toxicity is limited to cell lines expressing high levels of SARM1, a NAD glycohydrolase.
Giuseppe Ranieri   +5 more
wiley   +1 more source

RAD50 missense variants differentially affect the DNA damage response and mitotic progression

open access: yesFEBS Letters, EarlyView.
RAD50 incorporates into the MRN complex and initiates the DNA damage response. Furthermore, RAD50 promotes mitotic progression. RAD50 missense variants capable of forming an MRN complex supported the DNA damage response and mitotic features to different extents in complementation experiments, indicating these functions are separable and might impact ...
Hanna Redeker   +9 more
wiley   +1 more source

ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling

open access: yesMolecular Oncology, EarlyView.
We identified adaptor protein ShcD as upregulated in triple‐negative breast cancer and found its expression to be correlated with reduced patient survival and increased invasion in cell models. Using a proteomic screen, we identified novel ShcD binding partners involved in EGFR signaling pathways.
Hayley R. Lau   +11 more
wiley   +1 more source

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