Table of Contents
Research Articles
- Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension
The key pathogenic features of pulmonary hypertension are endothelial apoptosis and vascular inflammation, which are caused by the down-regulation of Amphiregulin, accompanied by HIF-1a and BAD-mediated up-regulation of the target genes such as RRP1B, PHB2, and NCOA6.
- Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome
The authors use photocrosslinking activity-based probes to monitor RNF12/RLIM E3 ubiquitin ligase activity and report the impact of Tonne-Kalscheuer syndrome (TOKAS) patient variants on catalysis.
- Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants
Analysis of ALS patient-derived and engineered cells revealed that mutant UBQLN2 increases mRNA and protein of MAP1B which is mediated by dephosphorylation of FUS within its RNA-binding domain.
- Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models
This study offers new Caenorhabditis elegans models in which feeding with α-synuclein pre-formed fibrils results in prion-like aggregation of host α-synuclein and dopamine neuron degeneration, and these disease phenotypes are regulated by the heparan sulfate proteoglycan pathway.
- Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
This study demonstrates that the muscular dystrophy-associated proteins dystrophin, utrophin, dysferlin, and calpain-3 localize to the centrosome and that their absence leads to excess centrosomes, compromised nuclear morphology, impaired centrosome orientation, and defective microtubule nucleation.
- CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7
The structure of mammalian V-ATPase with mEAK-7 shows how a TLDc domain-containing protein can bind the proton pump to form an activity-sensitive interaction.
- Identification and characterization of a membrane receptor that binds to human STC1
A study using TriCEPS-based ligand–receptor methodology and surface plasmon resonance assays identified that human stanniocalcin-1 binds to insulin-like growth factor-2 receptors in human leukemia monocytic cells with high affinity.
- KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cells
Depletion of the centrosomal kinesin KIF24, known to restrain the assembly of primary cilia, suppresses multipolar spindle formation by clustering centrosomes in centrosome-amplified PDAC cells.
- STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer
Using a dual recombinase mouse model of pancreatic cancer, investigators uncover genetic evidence for the role of STAT3 signaling in cancer-associated fibroblasts in promoting tumor progression and an immunosuppressive microenvironment.
- PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance
PVT1 is a YAP1 dependent stress responsive lncRNA that promotes ovarian cancer metastasis and chemoresistance, making PVT1 a promising therapeutic target.
- Lack of bombesin receptor–activated protein attenuates bleomycin-induced pulmonary fibrosis in mice
Enhanced autophagic activity in fibroblasts due to lack of BRAP homologous protein might contribute to the resistance to pulmonary fibrosis in mice.
- The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program
The MLL3/4 histone methyltransferase complexes and the histone deacetylase complex MiDAC regulate the histone mark H4K20ac to calibrate gene expression of a common set of target genes.
- ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF
There are at least 14 AM subtypes; their frequency, along with other immune cells, is highly conserved across individuals, suggesting a specific niche exists for each leukocyte population.
- ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1
As a mechanism of crosstalk, potentially relevant to cancer and developmental signaling, ERK2 MAP kinase phosphorylates the Hedgehog-pathway transcription factor GLI1 on three sites, promoting release of the negative regulator SUFU and the consequent activation of GLI1.
- Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity
The authors provide the first description of the impact of reducing pdzd8-mediated mito–ER contacts which prolongs lifespan, reduces age-related locomotor decline, and protects against mitochondrial toxins. pdzd8 loss is also protective against neuronal toxicity from Aβ42.