Endoplasmic Reticulum Stress and Disease

Target deconvolution of an insulin hypersecretion-inducer acting through VDAC1 with a distinct transcriptomic signature in beta-cells

This paper identifies VDAC1 as the target of SW016789, a hypersecretion inducer, and shows it causes distinct transcriptomic changes in beta-cells compared to ER stress.

Integrin-Specific Signaling Drives ER Stress-Dependent Atherogenic Endothelial Activation

This study shows fibronectin-binding integrins drive ER stress in endothelial cells under atherogenic conditions, promoting inflammation through JNK-c-Jun signaling.

AMFR provides an ERAD bypass mechanism to maintain proteostasis under canonical E3 ligase deficiency

The paper identifies AMFR as a compensatory factor for ERAD pathway function when RNF5/185 is deficient, showing its role in degrading mutant CFTR.

Inositol-Requiring Enzyme 1 Pathway and Autophagy Drive Sequential Response of Endothelial Cells to Febrile Range Hyperthermia

This study investigates how human coronary artery endothelial cells respond to fever-range hyperthermia, finding that the IRE1-autophagy pathway regulates cell function and integrity.

IRE1α and IRE1β Protect Intestinal Epithelium and Suppress Colorectal Tumorigenesis through Distinct Mechanisms

This study investigates the roles of IRE1α and IRE1β in intestinal epithelial cells, showing they protect against colorectal tumorigenesis through distinct mechanisms.

Activation of the endoplasmic reticulum stress regulator IRE1α compromises pulmonary host defenses

This study shows that activating IRE1α in the lungs during MRSA infection worsens pneumonia by increasing inflammation and cell death, but blocking IRE1α improves survival and reduces lung damage.

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

This study shows that KUS121 reduces atherosclerosis by maintaining ATP levels and reducing ER stress in endothelial cells.

A common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice

This paper shows a CTRB2 deletion variant increases pancreatic cancer risk by causing ER stress and inflammation in mice, using a new genetic model.

A structural basis for chaperone repression of stress signalling from the endoplasmic reticulum

This study identifies how AGR2 chaperone forms a dimer to repress IRE1β dimerization and suppress the UPR by blocking its activating conformation.

TMED9 coordinates the clearance of misfolded GPI-anchored proteins out of the endoplasmic reticulum and into the Golgi

This study shows TMED9 facilitates the ER-to-Golgi transport of misfolded GPI-anchored proteins via the RESET pathway, with its function regulated by BRD4780.

Application of Whole Proteome Thermal Shift Assays to Define PERK-dependent Changes in Protein Homeostasis during the Unfolded Protein Response

The paper uses proteomics and PISA analysis to study PERK-dependent changes in protein homeostasis during ER stress induced by tunicamycin.

Phenylhydrazone-based Endoplasmic Reticulum Proteostasis Regulator Compounds with Enhanced Biological Activity

This study identifies AA263 analogs that enhance ER proteostasis by targeting ER protein disulfide isomerases, correcting protein misfolding in disease models.

Identification of Omaveloxolone as An Endoplasmic Reticulum Associated Degradation Inhibitor That Induces Early Apoptotic Signaling in Multiple Myeloma

This paper identifies omaveloxolone as an ERAD inhibitor that induces apoptosis in multiple myeloma cells through caspase 8 and DISC signaling.

Dual regulation of the unfolded protein response by IGF2BP3 during ER stress

This study shows IGF2BP3 regulates UPR effectors by stabilizing transcriptional regulators and destabilizing UPR target mRNAs during ER stress, modulating the UPR response.

NEMF-mediated CAT-tailing defines distinct branches of translocation-associated quality control

The paper identifies NEMF-mediated CAT-tailing as a mechanism that directs substrates through distinct degradation pathways during translocation-associated quality control.

Analysis of patient data reveals novel cancer-relevant functions for GCN2/eIF2αK4

The paper correlates GCN2 expression with genes involved in stress responses, mitosis, and cell migration in cervical cancer samples, revealing novel cancer-relevant functions.

Dysregulation of FicD AMPylation causes diabetes by disrupting pancreatic endocrine homeostasis

This study shows that a mutation in FicD causes diabetes by disrupting BiP AMPylation and pancreatic endocrine homeostasis in mice.

Natural SEL1L variants modify ERAD, proteasome function, and survival in a Drosophila model of NGLY1 deficiency

Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation

This study identifies two small molecule inhibitors of FICD that suppress both endogenous and pathologic protein AMPylation, improving proinsulin processing in β cells.

Harnessing the Evolution of Proteostasis Networks to Reverse Cognitive Dysfunction

This study investigates how a genetic variant disrupts proteostasis networks, leading to cognitive dysfunction, and identifies a viral protein that can reverse these deficits.

Mapping the ISR Landscape in Cognitive Disorders via single-cell multi-omics

The paper generates a single-cell ISR atlas in a mouse model of persistent ISR activation, identifying cell-type-specific ISR programs and their roles in cognitive decline.

Lineage plasticity of the integrated stress response is a hallmark of cancer evolution.

This study shows that activation of the integrated stress response (ISR) drives tumor evolution and therapy resistance by promoting dedifferentiation and stemness in lung adenocarcinoma.

Initiation of ERAD by the bifunctional complex of Mnl1 mannosidase and protein disulfide isomerase

The paper shows the Mnl1-Pdi1 complex initiates ERAD by de-mannosylating misfolded proteins and reducing their disulfides, enabling translocation for proteasomal degradation.

Mechanism of counterattack against eIF2α kinase immune signalling by viral pseudo-kinase PK2

This study reveals how viral pseudo-kinase PK2 inhibits host eIF2 kinase by binding to and blocking its regulatory subdomain, providing insights into viral immune evasion strategies.

Dynamic modulation of IRE1α-XBP1 signaling by adenovirus

This study shows that adenovirus serotype 5 modulates IRE1α-XBP1 signaling by activating IRE1 but blocking XBP1s production, revealing a novel antiviral mechanism evaded by the virus.

PEBP1 amplifies mitochondrial dysfunction induced integrated stress response

This study identifies PEBP1 as a mediator of mitochondrial stress response by enhancing eIF2 phosphorylation and ISR gene expression.

C-terminal domain mobility underpins substrate engagement by the Chaetomium thermophilum EDEM:PDI ERAD-L checkpoint complex

The paper determines Cryo-EM structures of the EDEM:PDI complex with and without a substrate, revealing how disulfide bonds regulate conformational changes essential for substrate engagement.

Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung Derived Cell Lines

This study compares how three betacoronaviruses interact with the PERK pathway of the integrated stress response, showing differences in their reliance on eIF2 dephosphorylation for replication.

Trazodone, dibenzoylmethane and tauroursodeoxycholic acid do not prevent motor dysfunction and neurodegeneration in Marinesco-Sjögren syndrome mice

This study tests trazodone, dibenzoylmethane, and tauroursodeoxycholic acid in MSS mice but finds no prevention of motor dysfunction or neurodegeneration.

The MAP kinase scaffold MORG1 shapes cell death in unresolved ER stress in Arabidopsis

The paper identifies MORG1 as a regulator of ER stress tolerance in Arabidopsis by modulating MPK6-dependent phosphorylation of WRKY8, revealing a signaling axis that fine-tunes UPR gene expression.