Molecular Cell
@cp-molcell.bsky.social
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📥 15
📝 434
Molecular Cell is a Cell Press journal that aims to publish the best papers in molecular biology.
pinned post!
Read the latest issue here:
www.cell.com/molecular-ce...
4 days ago
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A mechanism of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence
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A mechanism of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence
Single-molecule fluorescence microscopy studies by Zhou et al. show that transcription activator proteins bind at UAS/enhancer DNA and then sequentially or simultaneously recruit Mediator coactivator and RNA polymerase II to form an initiation complex precursor. Multiple DNA-bound activators synergistically enhance recruitment by binding to the same Mediator complex.
http://dlvr.it/TPBbzw
about 4 hours ago
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The Piwi-piRNA complex initiates transposon silencing via transcription termination factors PNUTS and Senataxin
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The Piwi-piRNA complex initiates transposon silencing via transcription termination factors PNUTS and Senataxin
Wu et al. reveal that the SFiNX complex triggers transposon silencing through the association of Sov with two transcription termination factors, PNUTS and Senataxin, leading to RNA Pol II stalling. These findings suggest that piRNAs function as transcription termination signals, initiating piRNA-guided repression prior to transposon heterochromatinization.
http://dlvr.it/TPBT1R
about 8 hours ago
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4
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Transcription-replication conflict resolution by nuclear RNA interference
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Transcription-replication conflict resolution by nuclear RNA interference
Nuclear RNA interference limits genome instability beyond centromere function, though the mechanism was largely unknown. In this study, Cheng et al. discovered that, in S. pombe, Dicer (Dcr1) terminates RNA polymerase II at promoter-proximal pause sites when R-loops accumulate, which would otherwise cause head-on collision with the replication machinery.
http://dlvr.it/TPBFZ6
about 12 hours ago
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Dcr1 senses R-loops for RNAPII termination at sites of replication stress and repair pathway choice
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Dcr1 senses R-loops for RNAPII termination at sites of replication stress and repair pathway choice
To maintain genome stability, the fundamental processes of transcription, replication, and DNA repair must be tightly coordinated. Wang et al. identify the RNA processing protein Dcr1 as a molecular hub that connects these processes, resolving transcription blocks to prevent replication fork collapse and directing the choice of high-fidelity DNA repair.
http://dlvr.it/TPB0m2
about 15 hours ago
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A structural basis for chaperone repression of stress signaling from the endoplasmic reticulum
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A structural basis for chaperone repression of stress signaling from the endoplasmic reticulum
Neidhardt et al. uncover a structural basis for a long-standing concept: unfolded proteins activate stress signaling by competing for limited chaperones. Studying AGR2 and IRE1β, they reveal how chaperone binding disrupts the assembly of the active state of the stress transducer, providing a detailed view of cellular stress regulation.
http://dlvr.it/TP9Jz6
1 day ago
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Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins
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Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins
mitoRQC protects mitochondria against toxic CAT-tailed proteins. Using a genome-wide screen, Bertram et al. identify Pth2 as a peptidyl-tRNA hydrolase within mitoRQC. Pth2 modulates the import of CAT-tailed proteins and their access to the cytosolic QC network. Other hits from the screen show that, generally, delayed import protects mitochondria against toxic CAT-tailed proteins.
http://dlvr.it/TP8ZqC
2 days ago
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Sequential verification of transcription by Integrator and Restrictor
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Sequential verification of transcription by Integrator and Restrictor
Estell and Łazowski et al. show that Integrator and Restrictor form distinct pathways for early attenuation of RNA polymerase II: Integrator acts at the promoter-proximal pause site, whereas Restrictor acts over a downstream “restriction zone.” For transcription to proceed, CDK7/9 oppose Integrator, while U1 snRNP counteracts both Integrator and Restrictor.
http://dlvr.it/TP82Xm
3 days ago
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3
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Mechanisms of assembly and function of the Hsp70-Hsp40 chaperone machinery
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Mechanisms of assembly and function of the Hsp70-Hsp40 chaperone machinery
Jiang et al. determine the architecture of the Hsp70-Hsp40 complex and reveal how dynamic interactions between the two chaperones regulate protein refolding. These findings illuminate a central mechanism in cellular quality control and stress protection.
http://dlvr.it/TP7vN1
3 days ago
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1
1
Productive mRNA chromatin escape is promoted by PRMT5 activity
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Productive mRNA chromatin escape is promoted by PRMT5 activity
DeAngelo et al. show that PRMT5 methylation of Sm protein tails prevents snRNPs and intron-rich RNAs from being trapped on chromatin. Fractionated transcriptomics and proteomics reveal that PRMT5 activity ensures splicing completion and release of mature transcripts for productive nuclear export.
http://dlvr.it/TP7gn6
3 days ago
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Tuning insulin receptor signaling using de novo-designed agonists
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Tuning insulin receptor signaling using de novo-designed agonists
Wang, Cardoso, and Cai et al. design synthetic insulin receptor agonists that impose distinct receptor conformations, leading to modulated signaling. These agonists outperform insulin in metabolic control, remain active on disease-causing mutants, and reduce mitogenic responses, providing insight into how receptor conformations shape signaling outcomes and enabling safer insulin-like therapeutics.
http://dlvr.it/TP7QNZ
4 days ago
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SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis
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SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis
Dias et al. discover that the orphan solute carrier protein, SLC25A45, enables mitochondrial import of methylated amino acids. SLC25A45-dependent mitochondrial uptake of trimethyllysine drives carnitine biosynthesis. Mutation near its C terminus impacts SLC25A45 proteostasis and associates with altered methylated amino acid levels in human plasma.
http://dlvr.it/TP6vX2
4 days ago
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Mechanism of DNA entrapment by a loop-extruding Wadjet SMC motor
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Mechanism of DNA entrapment by a loop-extruding Wadjet SMC motor
Wadjet is an SMC-based prokaryotic defense system that eliminates plasmid DNA. Roisné-Hamelin et al. present structures capturing key steps of its DNA-loading mechanism. This work reveals how Wadjet topologically entraps DNA by SMC dimer rotation around DNA and defines the starting point of loop extrusion by the SMC motor.
http://dlvr.it/TP6lZ8
4 days ago
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Read the latest issue here:
www.cell.com/molecular-ce...
4 days ago
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Online Now: Metabolic environment-driven remodeling of mitochondrial ribosomes regulates translation and biogenesis Online now:
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Metabolic environment-driven remodeling of mitochondrial ribosomes regulates translation and biogenesis
Zheng et al. demonstrate that mitochondria remodel the structure and composition of mitochondrial ribosomes in response to metabolic state. This structural “gear-switching” mechanism fine-tunes mitochondrial translation and biogenesis, compensating for the absence of dedicated signaling pathways within mitochondria.
http://dlvr.it/TP6WJ8
4 days ago
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Online Now: Phage SSB detection by retron Eco8 msDNA unleashes nuclease-mediated immunity Online now:
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Phage SSB detection by retron Eco8 msDNA unleashes nuclease-mediated immunity
The cryo-EM structure of the retron Eco8 system reveals an autoinhibited 4:4:4 complex of RT, msDNA, and OLD nuclease. Phage SSB binding to msdDNA unleashes non-specific nuclease activity to restrict phage replication, establishing msDNA as a molecular switch for Eco8 activation.
http://dlvr.it/TNzMdP
11 days ago
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Online Now: Molecular mechanism of Eco8-mediated anti-phage defense Online now:
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Molecular mechanism of Eco8-mediated anti-phage defense
Yuan et al. uncover how the bacterial defense system Eco8 detects and combats phage infection. Through structural and biochemical analyses, they show that phage ssDNA-binding proteins trigger Eco8 activation, conferring broad-spectrum immunity. This work highlights msDNA as both a structural component and a phage sensor in antiviral defense.
http://dlvr.it/TNz7LF
12 days ago
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Online Now: The Piwi-piRNA complex initiates transposon silencing via transcription termination factors PNUTS and Senataxin Online now:
loading . . .
The Piwi-piRNA complex initiates transposon silencing via transcription termination factors PNUTS and Senataxin
Wu et al. reveal that the SFiNX complex triggers transposon silencing through the association of Sov with two transcription termination factors, PNUTS and Senataxin, leading to RNA Pol II stalling. These findings suggest that piRNAs function as transcription termination signals, initiating piRNA-guided repression prior to transposon heterochromatinization.
http://dlvr.it/TNyGhP
12 days ago
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Online Now: The E3 ligase RNF32 controls the IκB kinase complex and NF-κB signaling in intestinal stem cells Online now:
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The E3 ligase RNF32 controls the IκB kinase complex and NF-κB signaling in intestinal stem cells
Lauriola, Enriqué Steinberg, et al. report that RNF32, a ubiquitin ligase enriched in intestinal stem cells, links calcium levels to NF-κB signaling by activating the IKK complex. This study uncovers a calcium-dependent mechanism involved in responses to bacterial stimuli, revealing how intestinal cells integrate signaling cues to regulate intestinal homeostasis.
http://dlvr.it/TNy2k6
13 days ago
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Online Now: Transcription-replication conflict resolution by nuclear RNA interference Online now:
loading . . .
Transcription-replication conflict resolution by nuclear RNA interference
Nuclear RNA interference limits genome instability beyond centromere function, though the mechanism was largely unknown. In this study, Cheng et al. discovered that, in S. pombe, Dicer (Dcr1) terminates RNA polymerase II at promoter-proximal pause sites when R-loops accumulate, which would otherwise cause head-on collision with the replication machinery.
http://dlvr.it/TNxpN4
13 days ago
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Online Now: Dcr1 senses R-loops for RNAPII termination at sites of replication stress and repair pathway choice Online now:
loading . . .
Dcr1 senses R-loops for RNAPII termination at sites of replication stress and repair pathway choice
To maintain genome stability, the fundamental processes of transcription, replication, and DNA repair must be tightly coordinated. Wang et al. identify the RNA processing protein Dcr1 as a molecular hub that connects these processes, resolving transcription blocks to prevent replication fork collapse and directing the choice of high-fidelity DNA repair.
http://dlvr.it/TNxLL7
13 days ago
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Online Now: Accumulation of succinate suppresses de novo purine synthesis through succinylation-mediated control of the mitochondrial folate cycle Online now:
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Accumulation of succinate suppresses de novo purine synthesis through succinylation-mediated control of the mitochondrial folate cycle
Nengroo et al. show that succinate dehydrogenase (SDH) maintains purine synthesis. SDH inhibition elevates succinate, inducing SHMT2 succinylation that suppresses mitochondrial one-carbon flow and formate supply, thereby constraining purine assembly. Cancer cells compensate via purine salvage, and dual inhibition of SDH and salvage yields significant antiproliferative effects and suppresses tumor growth.
http://dlvr.it/TNxBtc
13 days ago
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reposted by
Molecular Cell
Ben-Sahra Lab
13 days ago
Excited to share our latest work out today in
@cp-molcell.bsky.social
, revealing a molecular link between succinate dehydrogenase and purine synthesis, connecting two fundamental metabolic pathways. Huge congratulations to the first author, Mushtaq Nengroo!
www.sciencedirect.com/science/arti...
!
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Accumulation of succinate suppresses de novo purine synthesis through succinylation-mediated control of the mitochondrial folate cycle
The de novo purine synthesis pathway is fundamental for nucleotide production, yet the role of mitochondrial metabolism in modulating this process rem…
https://www.sciencedirect.com/science/article/pii/S1097276525008196?dgcid=author
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Online Now: Cryo-EM reveals open and closed Asgard chromatin assemblies Online now:
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Cryo-EM reveals open and closed Asgard chromatin assemblies
Ranawat et al. show the cryo-EM structures of Asgard archaeal chromatin assemblies, revealing that the histone HHoB assembles into both compact closed and extended open hypernucleosomes. The closed conformation is conserved across archaea, while the open conformation represents an Asgard-specific innovation.
http://dlvr.it/TNwzRW
14 days ago
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reposted by
Molecular Cell
18 days ago
With funds from NIH,
@alsassociation.bsky.social
, and Target ALS Foundation, Macy Sprunger and Meredith Jackrel
@washu.edu
and collaborators purified and visualized Matrin-3, a major advance for studying the root causes of ALS. Findings published
@cp-molcell.bsky.social
.
bit.ly/4oAYHq3
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WashU chemists reveal new insights into ALS-linked protein
Using advanced biophysical and imaging techniques, Meredith Jackrel and her team have isolated Matrin-3 to better understand its role in neurodegenerative diseases.
http://bit.ly/4oAYHq3
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Online Now: A structural basis for chaperone repression of stress signaling from the endoplasmic reticulum Online now:
loading . . .
A structural basis for chaperone repression of stress signaling from the endoplasmic reticulum
Neidhardt et al. uncover a structural basis for a long-standing concept: unfolded proteins activate stress signaling by competing for limited chaperones. Studying AGR2 and IRE1β, they reveal how chaperone binding disrupts the assembly of the active state of the stress transducer, providing a detailed view of cellular stress regulation.
http://dlvr.it/TNrSVK
19 days ago
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Join us in Shenzhen, China (Nov 5–7, 2026) for #CellSymposia: Biological function in 3D: Structure, dynamics, and AI. in partnership wtith the Southern University of Science and Technology #CS3Dbiologicalfunction26
http://dlvr.it/TNqQwm
19 days ago
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Online Now: Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins Online now:
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Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins
mitoRQC protects mitochondria against toxic CAT-tailed proteins. Using a genome-wide screen, Bertram et al. identify Pth2 as a peptidyl-tRNA hydrolase within mitoRQC. Pth2 modulates the import of CAT-tailed proteins and their access to the cytosolic QC network. Other hits from the screen show that, generally, delayed import protects mitochondria against toxic CAT-tailed proteins.
http://dlvr.it/TNq6K4
20 days ago
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reposted by
Molecular Cell
Kranzusch Lab
26 days ago
Perfect timing in the field for a beautiful review on NAD+ in bacterial immunity by
@hugovaysset.bsky.social
and
@audeber.bsky.social
@cp-molcell.bsky.social
#MicroSky
www.cell.com/molecular-ce...
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reposted by
Molecular Cell
Mokranjac Lab
21 days ago
New publication alert!!!🥳 We identified Pth2 as a peptidyl tRNA hydrolase in the mitoRQC pathway! Thank you to all the co-authors!!
@cp-molcell.bsky.social
@dfg.de
@osman-lab.bsky.social
@lmumuenchen.bsky.social
doi.org/10.1016/j.mo...
#Pth2
#mitochondria
#mitoRQC
#qualitycontrol
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Online Now: Sequential verification of transcription by Integrator and Restrictor Online now:
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Sequential verification of transcription by Integrator and Restrictor
Estell and Łazowski et al. show that Integrator and Restrictor form distinct pathways for early attenuation of RNA polymerase II: Integrator acts at the promoter-proximal pause site, whereas Restrictor acts over a downstream “restriction zone.” For transcription to proceed, CDK7/9 oppose Integrator, while U1 snRNP counteracts both Integrator and Restrictor.
http://dlvr.it/TNpcvv
20 days ago
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Molecular mechanisms in innate immunity
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Molecular mechanisms in innate immunity
In the everlasting conflict between host species and invading pathogens, innate immunity provides an early line of defense. Comprising intrinsic defensive mechanisms, innate immune systems are found across the tree of life. There is a strong appreciation of the cell types contributing to innate immune responses and the pathways that enable their function. Excitingly, interest has turned to characterizing the underlying molecular mechanisms that drive cellular immune responses and to an emphasis on how the components work together to orchestrate this key aspect of host defense.
http://dlvr.it/TNpTNd
20 days ago
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Conversations at the interface of metabolism and immunity
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Conversations at the interface of metabolism and immunity
The developing field of immunometabolism showcases how molecular insights inform on cellular-level responses to both internal context and environmental stimuli. For our focus issue on innate immunity, we spoke with researchers about the new doors they see opening in this area, from molecular crosstalk to therapeutic potential.
http://dlvr.it/TNpFdw
21 days ago
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Split-site ubiquitination gives ZNFX1 new power in RNA defense
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Split-site ubiquitination gives ZNFX1 new power in RNA defense
Recent work by Grabarczyk et al. uncovers the molecular mechanism by which ZNFX1, an interferon-stimulated gene, employs a novel split-site E3 ligase domain structure to ubiquitinate both protein lysine residues and RNA 2′ hydroxyls. This activity enables ZNFX1 to compact pathogenic RNA into dense, ubiquitin-coated particles, revealing a new modality for interferon-induced antiviral defense.
http://dlvr.it/TNp0pb
21 days ago
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Sugar coats shield immunogenic RNA modification:A new function for RNA glycosylation
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Sugar coats shield immunogenic RNA modification:A new function for RNA glycosylation
A new function of glycosylated RNAs has been discovered by Graziano et al. in which the glycosylation of RNA molecules shields acp³U RNA modification from triggering innate immune responses.
http://dlvr.it/TNnXB5
21 days ago
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Caspase-8 loss stings the skin: STING drives necroptosis and interferonopathy
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Caspase-8 loss stings the skin: STING drives necroptosis and interferonopathy
In a recent Nature paper, Kelepouras et al. uncover how STING licenses ZBP1-driven necroptosis through transcriptional priming and Z-nucleic acid amplification, revealing a pathogenic circuit in SAVI and highlighting the ZBP1-RIPK3-MLKL axis as a therapeutic target.
http://dlvr.it/TNnP8G
21 days ago
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For our innate immunity focus issue, Hugo Vaysset and Aude Bernheim explore NAD+ in bacterial antiphage defense systems and host immune evasion and connect this metabolite to conserved domains in eukaryotic immune systems.
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The multifaceted roles of NAD+ in bacterial immunity
In this review, Vaysset and Bernheim examine how nicotinamide adenine dinucleotide (NAD+) is a key player in diverse and widespread bacterial antiphage defense systems and phage counterdefense. The authors finally highlight how NAD+-processing protein domains from antiphage systems are also conserved and involved in immunity in eukaryotic organisms.
http://dlvr.it/TNn9lL
22 days ago
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Amino acid and cholesterol metabolism in innate immunity
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Amino acid and cholesterol metabolism in innate immunity
Li et al. review the function and interplay between amino acids and cholesterol metabolites in innate immunity. They highlight how these metabolic pathways regulate immune cell function under both physiological and pathological conditions. In the conclusion, they also discuss emerging metabolic interventions for potential treatment against immune-related diseases.
http://dlvr.it/TNmwhz
22 days ago
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Metabolites in the extracellular tumor microenvironment and the shaping of macrophage function
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Metabolites in the extracellular tumor microenvironment and the shaping of macrophage function
Cancer cells rewire metabolism to survive harsh tumor environments, generating altered metabolites that profoundly influence macrophage plasticity in the tumor microenvironment. This review explores mechanistic insights and highlights emerging therapeutic strategies targeting tumor assosiate macrophage-metabolite crosstalk to improve clinical outcomes.
http://dlvr.it/TNmGCP
23 days ago
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RLRs detect foreign RNA during viral infection, yet RLRs can also sense endogenous RNAs. For our innate immunity focus issue, Mariska van Huizen and Michaela Gack discuss RLR-mediated sensing and pathway regulation.
http://dlvr.it/TNlZtC
24 days ago
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Activation and regulation of cGAS-STING signaling in cancer cells
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Activation and regulation of cGAS-STING signaling in cancer cells
Cancer-intrinsic genomic instability drives cytosolic DNA accumulation, triggering cGAS-STING immune signaling. Shim et al. review recent advances in cancer/cGAS-STING crosstalk, with a molecular-level focus on sources of cytosolic DNA and immunoregulatory mechanisms, including their therapeutic implications.
http://dlvr.it/TNl5CC
24 days ago
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In this innate immunity focus issue, Roy Parker and colleagues discuss how condensation of pattern recognition receptors (PRRs) with foreign nucleic acids is regulated in innate immune activation.
http://dlvr.it/TNkyJ0
24 days ago
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8
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Orchestration of plant PRR- and NLR-mediated immunity: Protein kinases and beyond
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Orchestration of plant PRR- and NLR-mediated immunity: Protein kinases and beyond
Plant PRR and NLR immune sensors detect pathogen cues and trigger robust yet balanced immune responses. Yan et al. discuss how diverse transmembrane and intracellular protein kinases integrate PRR- and NLR-mediated signaling through reciprocal potentiation and constraint, coordinating immune outputs that sustain infection resilience.
http://dlvr.it/TNklNN
25 days ago
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NLRP1 under pressure: An overview of the NLRP1 inflammasome as a sensor of cellular stress
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NLRP1 under pressure: An overview of the NLRP1 inflammasome as a sensor of cellular stress
Since its discovery several decades ago, the function and signaling mechanisms of the NLRP1 inflammasome have remained largely elusive. Yap et al. consolidate the breadth of NLRP1 findings, discuss its functions as a sensor of cellular stress and virus infection, and compare NLRP1 with functionally similar proteins, CARD8 and PIDD1.
http://dlvr.it/TNkWch
25 days ago
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S-Palmitoylation regulates signaling mediated by NLRP3 and other innate immune receptors
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S-Palmitoylation regulates signaling mediated by NLRP3 and other innate immune receptors
S-Palmitoylation regulates innate immune signaling by modulating the activation, assembly, and localization of key mediators such as NLRP3, GSDMD, NOD2, TLRs, STING, and MAVS. Varfolomeev et al. highlight the role of S-palmitoylation in inflammasome formation and inflammatory cell death while also addressing unresolved questions about its physiological significance and context-dependent effects.
http://dlvr.it/TNk3dT
25 days ago
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3
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For our focus issue on innate immunity, Ruochan Chen, Daolin Tang and colleagues discuss damage-associated molecular pattern (DAMP) release upon cell death and downstream immune pathways.
http://dlvr.it/TNjw54
25 days ago
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Cells must vigilantly sense and respond to invading pathogens and danger signals. This focus issue explores the interconnected pathways of innate immunity from a mechanistic perspective, delving into molecular insights into defense responses across the tree of life.
www.cell.com/molecular-ce...
25 days ago
1
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Cell-death networks
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Cell-death networks
Cells can undergo death through various genetically regulated pathways, each leading to distinct tissue outcomes. Emerging evidence suggests that these pathways are molecularly interconnected, indicating that the mode of death is determined not only by apical signals but by the availability of terminal executioners/substrates. This evolving understanding challenges the traditional rigid classification of cell death and has important implications for its therapeutic targeting in diseases.
http://dlvr.it/TNjhWV
26 days ago
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Online Now: PALB2 and 53BP1 govern post-resection homologous recombination DNA repair Online now:
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PALB2 and 53BP1 govern post-resection homologous recombination DNA repair
(Molecular Cell 85, 2824–2838.e1–e8; August 7, 2025)
http://dlvr.it/TNhJXx
27 days ago
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Online Now: Mechanisms of assembly and function of the Hsp70-Hsp40 chaperone machinery Online now:
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Mechanisms of assembly and function of the Hsp70-Hsp40 chaperone machinery
Jiang et al. determine the architecture of the Hsp70-Hsp40 complex and reveal how dynamic interactions between the two chaperones regulate protein refolding. These findings illuminate a central mechanism in cellular quality control and stress protection.
http://dlvr.it/TNgPtJ
28 days ago
0
5
3
Online Now: Productive mRNA chromatin escape is promoted by PRMT5 activity Online now:
loading . . .
Productive mRNA chromatin escape is promoted by PRMT5 activity
DeAngelo et al. show that PRMT5 methylation of Sm protein tails prevents snRNPs and intron-rich RNAs from being trapped on chromatin. Fractionated transcriptomics and proteomics reveal that PRMT5 activity ensures splicing completion and release of mature transcripts for productive nuclear export.
http://dlvr.it/TNfWFf
28 days ago
0
1
1
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