S. P. Gygi

Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST

This study uses nMOST to profile proteo-lipidomics in lysosomal storage disease mutants, revealing autophagy defects and mitochondrial dysfunction.

Inserting Pre-Analytical Chromatographic Priming Runs Significantly Improves Targeted Pathway Proteomics With Sample Multiplexing

The paper introduces GoDigViewer to optimize GoDig assays by implementing chromatographic priming runs, significantly improving peptide-level quantification success rates in targeted pathway proteomics.

Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays

This study uses proteome-wide thermal shift assays to analyze over a million thermal stability measurements from 96 compounds in cells and 70 in lysates, revealing target engagement and off-target effects.

Highly specific intracellular ubiquitination of a small molecule

The paper identifies a small molecule, BRD1732, that is ubiquitinated in cells, leading to proteasome inhibition through accumulation of ubiquitin chains.

Substrate identification and specificity profiling of deubiquitylases against endogenously-generatedubiquitin-protein conjugates

The paper identifies high-impact DUBs and their substrates using Xenopus egg extract and proteomics, revealing substrate characteristics influencing DUB specificity.

Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation

The paper demonstrates bidirectional substrate shuttling between the 26S proteasome and Cdc48 ATPase in yeast, showing how this process facilitates protein degradation.

Selective Mitochondrial Respiratory Complex I Subunit Deficiency Causes Tumor Immunogenicity

This study shows that deleting specific mitochondrial Complex I subunits, Ndufs4 and Ndufs6, enhances tumor immunogenicity and sensitivity to immune checkpoint blockade in mouse melanoma models.

Multifaceted proteome analysis at solubility, redox, and expression dimensions for target identification

The paper introduces PISA-REX, a high-throughput proteomics method combining redox, expression, and solubility analysis, and demonstrates its application in studying interferon responses in human monocytes and mice.

Fission yeast CK1 promotes DNA double-strand break repair through both homologous recombination and non-homologous end joining

This study shows that fission yeast CK1 orthologues Hhp1 and Hhp2 promote DNA double-strand break repair through both homologous recombination and non-homologous end joining by phosphorylating substrates like Arp8.

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease

This study uses transdifferentiated neurons to show lysosomal deficits are an early event in aging and Alzheimer's disease, leading to proteotoxic deposits and cell death.

Large-scale proteomic analysis of T. spiralis muscle-stage ESPs identifies a novel upstream motif for in silico prediction of secreted products

This study identifies a novel upstream motif in T. spiralis muscle-stage ESPs that can predict secreted proteins, using proteomic and computational methods.

RBM43 links adipose inflammation and energy expenditure through translational regulation of PGC1alpha

This study identifies RBM43 as a regulator of PGC1alpha translation, linking adipose inflammation to reduced energy expenditure and mitochondrial function in obesity.

UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation independently of the p97 ATPase

This study identifies UBXN1 as a negative regulator of the UPR that represses translation and maintains ER proteostasis independently of p97.

Phosphate Starvation Signaling Increases Mitochondrial Membrane Potential through Respiration-independent Mechanisms

The paper shows phosphate starvation increases mitochondrial membrane potential through respiration-independent mechanisms in yeast and mammalian cells.

Global proteome metastability response in isogenic animals to missense mutations and polyglutamine expansions in aging

This study examines how proteome conformational stability changes in aging C. elegans due to missense mutations and polyglutamine expansions, revealing age-dependent metastable protein networks.

The ancestral ESCRT protein TOM1L2 selects ubiquitinated cargoes for retrieval from cilia

The paper identifies TOM1L2 as a ciliary trafficking factor that recognizes K63-linked ubiquitin chains to retrieve ubiquitinated GPCRs from cilia.

Mapping the GALNT1 substrate landscape with versatile proteomics tools

This study identifies hundreds of novel GALNT1 substrates using proteomics tools, revealing preferences for Thr residues and Pro at positions +3 and +4, and implicating GALNT1 in diverse biological pathways.

An anaphase switch in astral microtubule dynamics specifically requires the APC/C-Cdc20-dependent degradation of the mitotic cyclin Clb4

The paper shows that APC/C-Cdc20-dependent degradation of Clb4 is required for the anaphase switch in astral microtubule dynamics, crucial for spindle orientation.

The relaxin receptor RXFP1 signals through a mechanism of autoinhibition

This study determines the cryo-EM structure of active-state RXFP1 bound to relaxin-2 and Gs protein, revealing an autoinhibition mechanism.

Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity

This paper introduces self-assembling short duplex RNAs that induce interferon production and inhibit multiple respiratory viruses.

Assessing target engagement using proteome-wide solvent shift assays

This paper develops solvent shift assays to assess target engagement using quantitative proteomics, showing they can identify compound targets and serve as a reliable alternative to existing methods.

Integrative analyses uncover mechanisms by which aging drives B cell lymphoma

This study identifies age-associated clonal B cells (ACBCs) as drivers of B-cell lymphoma in mice, linking aging-related epigenetic and cellular changes to cancer development and proposing mTOR/c-Myc inhibition as a therapeutic strategy.

Msp1/ATAD1 restores mitochondrial function in Zellweger Spectrum Disease

The paper investigates peroxisomal dysfunction in Zellweger Spectrum Disease and shows that overexpressing ATAD1 restores mitochondrial function in patient-derived fibroblasts.

DPP9 directly sequesters the NLRP1 C-terminus to repress inflammasome activation

This study identifies DPP9 as a repressor of NLRP1 inflammasome activation by sequestering the NLRP1 C-terminus, preventing inflammation during protein turnover.

Time-resolved proteomic profiling of the ciliary Hedgehog response reveals that GPR161 and PKA undergo regulated co-exit from cilia

The paper uses proximity labeling and mass spectrometry to profile ciliary proteome changes during Hedgehog signaling, identifying new proteins involved in ciliary exit and signaling regulation.

Rapid toxin sequestration modifies poison frog physiology

This study shows poison frogs rapidly accumulate toxins, altering protein abundance in immune response and small molecule transport across tissues.

Mitochondrial fatty acid synthesis coordinates mitochondrial oxidative metabolism

This study shows that mitochondrial fatty acid synthesis (mtFAS) regulates electron transport chain (ETC) complexes and skeletal myoblast differentiation, linking fatty acid synthesis to oxidative metabolism.

The insulin receptor adaptor IRS2 is an APC/C substrate that promotes cell cycle protein expression and a robust spindle assembly checkpoint

This study identifies IRS2 as an APC/C substrate, showing it regulates cell cycle protein expression and the spindle assembly checkpoint.

Global proteomics of Ubqln2-based murine models of ALS

The paper identifies proteomic changes in Ubqln2 mutant mice and finds that TRIM32, PEG10, and CXX1B are linked to UBQLN2 function and degradation.

Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes

This study identifies PfPP1 as essential for Plasmodium falciparum egress from host erythrocytes and shows it integrates internal and external signals for this process.