A5083069062- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Protein Degradation and Inhibitors
- Cellular transport and secretion
- Parkinson's Disease Mechanisms and Treatments
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Metabolomics and Mass Spectrometry Studies
- Autophagy in Disease and Therapy
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mass Spectrometry Techniques and Applications
- Microtubule and mitosis dynamics
- Bioinformatics and Genomic Networks
- NF-κB Signaling Pathways
- Photosynthetic Processes and Mechanisms
- Hedgehog Signaling Pathway Studies
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Fungal and yeast genetics research
- Chronic Lymphocytic Leukemia Research
- Biotin and Related Studies
Genentech
2025
Max Planck Institute of Biochemistry
2017-2024
Koç University
2015-2019
We previously reported that Parkinson’s disease (PD) kinase LRRK2 phosphorylates a subset of Rab GTPases on conserved residue in their switch-II domains (Steger et al., 2016) (PMID: 26824392). Here, we systematically analyzed the protein family and found 14 them (Rab3A/B/C/D, Rab5A/B/C, Rab8A/B, Rab10, Rab12, Rab29, Rab35 Rab43) to be specifically phosphorylated by LRRK2, with evidence for endogenous phosphorylation ten Rab43). Affinity enrichment mass spectrometry revealed primary...
The prevalence of Parkinson's disease (PD) is increasing but the development novel treatment strategies and therapeutics altering course would benefit from specific, sensitive, non-invasive biomarkers to detect PD early. Here, we describe a scalable sensitive mass spectrometry (MS)-based proteomic workflow for urinary proteome profiling. Our enabled reproducible quantification more than 2,000 proteins in 200 urine samples using minimal volumes two independent patient cohorts. was...
The recent revolution in computational protein structure prediction provides folding models for entire proteomes, which can now be integrated with large-scale experimental data. Mass spectrometry (MS)-based proteomics has identified and quantified tens of thousands posttranslational modifications (PTMs), most them uncertain functional relevance. In this study, we determine the structural context these PTMs investigate how information leveraged to pinpoint potential regulatory sites. Our...
Summary The global emergence of SARS-CoV-2 urgently requires an in-depth understanding molecular functions viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge COVID-19 pathophysiology 1–10 . Integration such datasets to obtain a holistic view virus-host define pathogenic properties is limited by heterogeneity experimental systems. We therefore conducted concurrent multi-omics study SARS-CoV. Using state-of-the-art...
Abstract Protein ubiquitination is involved in virtually all cellular processes. Enrichment strategies employing antibodies targeting ubiquitin-derived diGly remnants combined with mass spectrometry (MS) have enabled investigations of ubiquitin signaling at a large scale. However, so far the power data independent acquisition (DIA) regards to sensitivity single run analysis and completeness not yet been explored. Here, we develop sensitive workflow combining antibody-based enrichment...
The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs metabolic enzyme substrates. orthologous higher eukaryotic C-terminal to LisH (CTLH) complex has been proposed also recognize substrates through an alternative subunit, WDR26, which promotes the formation supramolecular CTLH assemblies. Here, we discover human WDR26 binds...
Abstract Exosomes, a type of small extracellular vesicles (sEVs), derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism which proteins are sorted to sEVs is not fully understood. Here, we report that ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as posttranslational modification (PTM) factor regulates sorting sEVs. We find UBL3 indispensable for MVBs also observe 60%...
Pathogenic mutations in the Leucine-rich repeat kinase 2 (LRRK2) are predominant genetic cause of Parkinson's disease (PD). They increase its activity, resulting augmented Rab10-Thr73 phosphorylation and conversely, LRRK2 inhibition decreases pRab10 levels. Currently, there is no assay to quantify levels for drug target engagement or patient stratification. To meet this challenge, we developed an high accuracy sensitivity targeted mass spectrometry (MS)-based determining stoichiometry human...
Reactivation of fetal hemoglobin expression by the downregulation BCL11A is a promising treatment for β-hemoglobinopathies. A detailed understanding BCL11A-mediated repression γ-globin gene (HBG1/2) transcription lacking, as studies to date used perturbations shRNA or CRISPR-Cas9 editing. We leveraged dTAG PROTAC degradation platform acutely deplete protein in erythroid cells and examined consequences nascent transcriptomics, proteomics, chromatin accessibility, histone profiling. Among 31...
Mitochondria are essential organelles whose dysfunction causes human pathologies that often manifest in a tissue-specific manner. Accordingly, mitochondrial fitness depends on versatile proteomes specialized to meet diverse requirements. Increasing evidence suggests phosphorylation may play an important role regulating functions and pathophysiology. Building recent advances mass spectrometry (MS)-based proteomics, we here quantitatively profile tissue along with their matching...
SARS-CoV-2 may directly and indirectly damage lung tissue other host organs, but there are few system-wide, untargeted studies of these effects on the human body. Here, we developed a parallelized mass spectrometry (MS) proteomics workflow enabling rapid, quantitative analysis hundreds virus-infected FFPE tissues. The first layer response to in all tissues was dominated by circulating inflammatory molecules. Beyond systemic inflammation, differentiated between true tissue-specific reflect...
Epithelial-mesenchymal transition (EMT) is driven by complex signaling events that induce dramatic biochemical and morphological changes whereby epithelial cells are converted into cancer cells. However, the underlying molecular mechanisms remain elusive. Here, we used mass spectrometry based quantitative proteomics approach to systematically analyze post-translational drive differentiation of human mammary (HMLE) mesenchymal. We identified 314 proteins out more than 6,000 unique 871...
T cell activation initiates protective adaptive immunity, but counterbalancing mechanisms are critical to prevent overshooting responses and maintain immune homeostasis. The CARD11-BCL10-MALT1 (CBM) complex bridges receptor engagement NF-κB signaling MALT1 protease activation. Here, we show that ABIN-1 is modulating the suppressive function of A20 in cells. Using quantitative mass spectrometry, identified as an interactor CBM signalosome activated counteract inducible human primary CD4...
Article19 April 2022Open Access Transparent process A GID E3 ligase assembly ubiquitinates an Rsp5 adaptor and regulates plasma membrane transporters Christine R Langlois Corresponding Author [email protected] orcid.org/0000-0003-1567-3577 Department of Molecular Machines Signaling, Max Planck Institute Biochemistry, Martinsried, Germany Contribution: Conceptualization, Data curation, Formal analysis, Supervision, Investigation, Methodology, Writing - original draft, review & editing Search...
E3 ligases regulate key processes, but many of their roles remain unknown. Using Perturb-seq, we interrogated the function 1,130 ligases, partners and substrates in inflammatory response primary dendritic cells (DCs). Dozens impacted balance DC1, DC2, migratory DC macrophage states a gradient maturation. Family members grouped into co-functional modules that were enriched for physical interactions specific programs through substrate transcription factors. E3s adaptors co-regulated same...
Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH ubiquitin ligases their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryoelectron microscopy (cryo-EM), biochemistry, cell biology reveal this...
COP1 and DET1 are components of an E3 ubiquitin ligase that is conserved from plants to humans. Mammalian binds a substrate adaptor for the CUL4A-DDB1-RBX1 RING ligase. Transcription factor substrates, including c-Jun, ETV4, ETV5, targeted proteasomal degradation effect rapid transcriptional changes in response cues such as growth deprivation. Here, we link homozygous R26W mutation lethal developmental abnormalities Experimental cryo-electron microscopy complex with DDB1 DDA1, well...
Article1 December 2020Open Access Transparent process Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis Özge Karayel orcid.org/0000-0003-2541-1159 Department Proteomics and Signal Transduction, Max Planck Institute Biochemistry, Martinsried, GermanyThese authors contributed equally to this work Search for more papers by author Peng Xu Hematology, St. Jude Children's Research Hospital, Memphis, TN, USAThese Isabell Bludau Germany Senthil...