João A. Paulo

GolgiFold: A Structural Predictome of Human Golgi Protein Complexes

The paper develops GolgiFold, a structure-based PPI map of human Golgi proteins, identifying over 1,800 interactions and confirming new protein contacts through experimental validation.

Structures of MyD88 and its oncogenic mutant reveal DNA binding with implications for cytosolic DNA sensing

This study reveals the structure of MyD88 and its oncogenic mutant, showing direct DNA binding and its role in innate immune responses.

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation

This study shows that lactate can be directly imported into mitochondria and oxidized to support cardiac energy production, independent of the pyruvate carrier.

Tumor suppressor-like mutations mark a dosage-constrained dependency in leukemia

The paper shows that oncogene-imposed dosage constraints can lead to mutations resembling tumor suppressor loss, which are essential in APL.

Aged white adipose tissue is rejuvenated in a young host through thermogenic remodeling of mature adipocytes

This study shows that old white adipose tissue can rejuvenate in young hosts through thermogenic remodeling and pathway activation, reversing biological age markers.

RNF185 destabilizes specific membrane proteins that span all ERAD branches

This study identifies RNF185 as a human ER-resident ubiquitin ligase that destabilizes membrane proteins with distinct aberrancies across all three ERAD branches.

Traffickome infers directed, compartment-resolved membrane trafficking from proteomic data

Traffickome infers directed membrane trafficking between cellular compartments from proteomic data, achieving high accuracy in predicting trafficking transitions.

Activation and inactivation pathways of a p53-like transcription factor govern lipid homeostasis in yeast

The paper identifies activation and inactivation pathways of Mga2, a p53-like transcription factor in yeast, showing its role in lipid homeostasis through regulation of Ole1 expression.

Components of an ESCRT-independent nuclear envelope assembly pathway

In S. japonicus, the ESCRT adaptor Alx1 activates the essential PH-domain protein Vid27 through interaction, driving postmitotic nuclear envelope sealing independently of Cmp7 and ESCRT-III.

2-Hydroxyglutarate Redirects Fatty Acid Partitioning to Mitigate Lipotoxic Stress and Preserve Metabolic Fuel

This paper shows that 2-hydroxyglutarate (2HG) alters fatty acid partitioning, reducing lipotoxic stress by shifting fatty acids toward storage and away from oxidation and membrane synthesis.

Structural Mechanisms of DNAJC13 Dimeric Assembly and InsP6 binding in Recycling Endosome Regulation

Cryo-EM at 2.4 Å shows DNAJC13 as an antiparallel arch-shaped homodimer with a buried InsP6 pocket; dimerization controls WASH recruitment, tubule fission, and melanin production.

Amino Acid Stress Induces Non-AUG Initiation of c-myc Translation

The paper shows that amino acid stress shifts c-myc translation from AUG-initiated to CUG-initiated isoforms via ribosome stalling and queue formation.

A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical and dopaminergic-like induced neurons

The paper develops a human stem cell toolkit for studying lysosomal storage disorders by generating proteomic data from induced cortical and dopaminergic-like neurons.

Activity-dependent lipid droplet biogenesis and turnover regulate synaptic integrity

This study identifies activity-dependent lipid droplet formation and lipophagy as critical regulators of synaptic integrity and neuronal function using a novel genetic reporter in cultured neurons and mouse motor cortex.

Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31

This study reveals how FBXO7 and PI31 regulate the proteasome 20S core particle and how disease variants disrupt this function.

CDK/mTOR-dependent phosphorylation of UBE2H restrains its charging with ubiquitin and regulates CTLH-dependent degradation

The paper identifies CDK/mTOR-dependent phosphorylation of UBE2H as a regulator of CTLH E3 ligase activity, showing how it controls ubiquitylation and substrate degradation.

Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease

The paper uses isogenic cortical organoids to identify variant-specific pathogenic pathways in Alzheimer's disease and demonstrates targeted interventions that restore neuronal survival.

Ribosome Quality Control Mitigates Proteotoxic Stress in Aneuploid Cells

The paper shows that ribosome quality control via ZNF598 degradation helps aneuploid cells survive proteotoxic stress, with ZNF598 expression linked to tumor aneuploidy.

A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform

The paper identifies SWIFT, a SWI/SNF subunit domain that mediates transcription factor interactions, showing its role in chromatin targeting and cancer cell proliferation.

miRISC inhibition causes mitotic defects and synergizes with genotoxic agents in cancers

The paper shows that inhibiting the HMWR complex causes mitotic defects and enhances cancer cell vulnerability when combined with genotoxic agents.

Pre-clinical validation of a novel AAV-mediated gene therapy for KCNV2 retinopathy improves visual function in a mouse model and expression in patient organoids

This paper demonstrates that AAV-mediated gene therapy restores retinal function and KCNV2 expression in a mouse model of KCNV2 retinopathy and human retinal organoids.

Harmine Selectively Drives Human Beta Cell Differentiation and Function Via Protein Kinase A Pathways

This paper shows harmine, a DYRK1A inhibitor, selectively promotes human beta cell differentiation and function via PKA activation, distinct from other DYRK1A inhibitors.

Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in dedifferentiated endometrial carcinomas

This study identifies shifted mSWI/SNF subcomplex stoichiometry in DDEC/UEC cancers and shows that SMARCA4/2 inhibitors reduce tumor growth and synergize with chemotherapy.

Promoter hijacking by primate LINC00473 disrupts an ancestral CREB-PDE10A feedback loop

The paper investigates how the primate-specific lncRNA LINC00473 disrupts an ancestral CREB-PDE10A feedback loop by hijacking its promoter.

Deazaguanylation is a nucleobase-protein conjugation required for type IV CBASS immunity

The paper identifies 7-deazapurine protein conjugation as essential for type IV CBASS immunity, revealing the roles of Cap9 and Cap10 in this process.

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias

This study identifies MECOM's role in blocking differentiation via CEBPA repression, showing that targeting this regulatory element can promote differentiation and reduce leukemia burden in AMLs.

Muscle-specific increased expression of JAG1 improves skeletal muscle phenotype in dystrophin-deficient mice.

This study shows that increasing JAG1 expression in dystrophin-deficient mice improves muscle size, strength, and myofiber number.

Next-Generation Multiplexed Targeted Proteomics Quantifies Post-Translational Modifications, Compound-Protein Interactions, and Disease Biomarkers with High Throughput

GoDig 2.0 improves targeted proteomics by increasing multiplexing, efficiency, and target coverage, enabling analysis of post-translational modifications and compound-protein interactions.

Neuronal activity triggers widespread changes in RNA stability

The paper shows neuronal activity affects RNA stability, with HuD regulating mRNA abundance and variants linked to neurodevelopmental disorders disrupting this process.

Catalytic pocket of Clr4 (Suv39h) methyltransfer-ase serves as a substrate receptor for Cullin 4-dependent histone H3 ubiquitination

This study shows that the catalytic pocket of Clr4 (Suv39h) acts as a receptor for Cul4-dependent H3K14 ubiquitination, which regulates Clr4's methylation activity on H3K9.