Endoplasmic Reticulum Stress and Disease

The UPR drives gametogenesis via an unexpected response, coordinating translation and ER structure

The paper shows that the endogenous UPR in budding yeast is essential for gametogenesis, coordinating translation and ER structure through a distinct mechanism from exogenous UPR activation.

Dfm1 promotes Ste24-dependent translocon quality control

This study identifies Dfm1 as a key factor in Ste24-dependent translocon quality control, showing that its loss increases toxicity of clogged translocon substrates.

Single-Nuclei Analysis of the Unfolded Protein Response (SNUPR): A Novel Method revealing bortezomib resistance mechanisms in Multiple Myeloma

SNUPR enables single-cell UPR profiling and reveals the role of IRE-1 axis in predicting bortezomib resistance in multiple myeloma.

Ergosterol acts as a permissive regulator of Ire1 responsiveness during ER stress

This study shows ergosterol modulates Ire1 activation during ER stress by adjusting UPR response amplitude, not directly triggering the pathway.

Stable Hrd1 tetramers at the heart of the retrotranslocon in living cells

This study uses single-molecule imaging to show that Hrd1 forms stable tetramers in the ER, revealing a conserved hydrophobic motif critical for dislocation.

Nuclear Receptor Liver Receptor Homolog-1 drives Intestinal Stem Cell regeneration and UPR/ER stress response after gut injury

This study identifies LRH-1 as essential for intestinal stem cell regeneration and ER stress response after gut injury, revealing its role in sustaining the IRE1-XBP1 UPR pathway.

De novo design of protein binders that target DELE1 to inhibit the mitochondrial stress response

This paper designs de novo proteins that bind DELE1, block its oligomerization, and inhibit the mitochondrial stress response in cells.

CHOP promotes the transition to chronic integrated stress response signaling with suppression of hepatocyte identity

This study shows CHOP promotes chronic integrated stress response signaling and suppresses hepatocyte identity in vivo by exacerbating ER stress and altering gene regulation.

Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline

The paper identifies a pyrazolopyridine alkaloid, S88, that reduces ER stress and age-related decline in neuronal and Drosophila models.

Targeting the IRE1α-XBP1 signaling axis impairs tumor growth and promotes myogenic differentiation in rhabdomyosarcoma

This study shows that inhibiting the IRE1α-XBP1 signaling pathway reduces tumor growth and promotes differentiation in rhabdomyosarcoma.

A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response

The paper identifies a chemical inhibitor of eIF2B that activates the Integrated Stress Response by stabilizing an inhibitory complex with phosphorylated eIF2.

Coronavirus M proteins disperse the trans-Golgi network and inhibit anterograde protein trafficking in the secretory pathway

This study shows that coronavirus M proteins disrupt the trans-Golgi network and inhibit anterograde protein trafficking in the secretory pathway, without affecting virus egress.

An atypical E3 ligase safeguards the ribosome during nutrient stress

This study identifies HOIL-1 as an atypical E3 ligase that protects the ribosome during nutrient stress, revealing a new signaling pathway involved in cell fate decisions.

In-cell structural insights into fungal ER stress responses

This study uses structural biology techniques to show that ER stress in yeast increases inactive ribosomes and modulates elongation factors, suggesting modest translation inhibition as a stress response.

ATF4-dependent upregulation of Bruno 1 remodels P-bodies to selectively protect mRNAs during ER stress throughout Drosophila melanogaster oogenesis

Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk

The paper identifies gene regulators of ER stress in beta cells and links them to type 2 diabetes risk through functional genomics and CRISPR screening.

Optogenetic Control of the Integrated Stress Response Limits Glioblastoma Invasion

This study uses optogenetic ISR activation to show reduced glioblastoma invasion and migration, suggesting potential therapeutic strategies.

Sexually dimorphic ATF4 expression in the fat confers female stress tolerance in Drosophila melanogaster

This study identifies sex-specific ATF4 expression in Drosophila fat tissue that contributes to female stress tolerance during nutrient deprivation.

Apollo-IRE1: A Genetically Encoded Sensor for Live Cell and Multiplexed Imaging of ER Stress

Apollo-IRE1 is a genetically encoded sensor that detects ER stress by measuring IRE1 oligomerization and fluorescence anisotropy changes, enabling multiplexed imaging in living cells.

RNF25 restrains GCN2 hyperactivation to sustain protein synthesis and cell proliferation in response to RNA damage

This study identifies RNF25 as a regulator of GCN2 activity during RNA damage, showing that RNF25 prevents excessive GCN2 activation to maintain protein synthesis and cell proliferation.

Ribonuclease L Regulates Antiviral Responsiveness through Cleavage of XBP1 mRNA

The paper shows RNase L suppresses XBP1s, which fine-tunes antiviral responses by negatively regulating RIG-I-like receptors, RNase L, and PKR pathways.

Mathematical modelling of mutant glycoprotein fate in the ER

The paper models the fate of mutant glycoproteins in the ER using an ODE framework to compare the effects of UGGT and ER mannosidase inhibition on ERQC and ERAD dynamics.

ATF4 and EcR interact to mediate both transcriptional activation and repression in the Drosophila fat body

This study shows ATF4 interacts with EcR to both activate and repress lipid metabolism genes in Drosophila fat body under homeostasis and stress conditions.

Aging promotes lung cancer metastasis through epigenetic ATF4 induction

This study shows aging promotes KRAS-driven lung cancer metastasis via ATF4 induction, which can be inhibited by glutaminase blockade.

IRE1 drives a homeostatic response to reduced protein influx into the endoplasmic reticulum

The paper identifies a third mode of IRE1 activation called TRES, triggered by reduced protein influx into the ER, leading to a distinct gene expression program to rebalance ER load.

ER Stress-Induced beta-Cell Apoptosis is Linked to Novel Select Lipid Signaling at the Transcriptional Level: Implications in T1D Development

This study identifies a novel lipid signaling pathway involving iPLA2β that links ER stress to β-cell apoptosis in T1D, revealing transcriptional regulation by iDLs and potential therapeutic targets.

Inhibition of FicD-mediated AMPylation and deAMPylation by Isoprenoid Diphosphates

This study identifies geranyl- and farnesyl-pyrophosphate as FicD inhibitors that differentially affect disease-causing variants, providing insights for therapeutic targeting of UPR.

Derlin-mediated ERAD of lipid regulator ORMDL3 safeguards mitochondrial function

This study shows Derlin-mediated ERAD of ORMDL3 prevents mitochondrial dysfunction by maintaining sphingolipid homeostasis and ER-mitochondria contact sites.

Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by ATF4 following optic nerve injury

This study shows ATF4, activated by PERK, coordinates both neurodegenerative and regenerative responses after optic nerve injury in mice.

SEL1L-HRD1 ER-Associated Degradation Facilitates Prohormone Convertase 2 Maturation and Glucagon Production in Islet α Cells

This study identifies SEL1L-HRD1 ERAD as a regulator of PC2 maturation and glucagon production in islet α cells by degrading misfolded proPC2.