0000000000925801

AUTHOR

Jörg Tatzelt

0000-0001-5017-5528

showing 2 related works from this author

A protein quality control pathway regulated by linear ubiquitination.

2019

Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence doma…

MaleHuntingtinSp1 protein humanProtein aggregationHTT protein humanDeubiquitinating enzymegenetics [Huntington Disease]Micegenetics [Sp1 Transcription Factor]0302 clinical medicineUbiquitinpathology [Brain]Valosin Containing Proteincytology [Fibroblasts]pathology [Neurons]PolyubiquitinCells CulturedMice Knockout0303 health sciencesHuntingtin ProteinGeneral NeuroscienceNF-kappa Bgenetics [Huntingtin Protein]Middle AgedCell biologymetabolism [Polyubiquitin]pathology [Huntington Disease]metabolism [Neurons]metabolism [NF-kappa B]Protein foldingFemalemetabolism [Fibroblasts]Protein BindingSignal TransductionAdultmetabolism [Valosin Containing Protein]Sp1 Transcription Factorcytology [Embryo Mammalian]genetics [Valosin Containing Protein]BiologyGeneral Biochemistry Genetics and Molecular Biologymetabolism [Sp1 Transcription Factor]03 medical and health sciencesddc:570Gene silencingAnimalsHumansmetabolism [Huntington Disease]Protein Interaction Domains and MotifsMolecular Biologymetabolism [Embryo Mammalian]030304 developmental biologyAgedSp1 transcription factorGeneral Immunology and MicrobiologyUbiquitinationProteotoxicitymetabolism [Brain]Case-Control Studiesmetabolism [Huntingtin Protein]biology.proteinProtein Processing Post-Translational030217 neurology & neurosurgerygenetics [NF-kappa B]
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The RAB GTPase RAB18 modulates macroautophagy and proteostasis

2017

Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins. Thus, the RAB GTPase RAB18 is a positi…

0301 basic medicineRecombinant Fusion Proteinsrab3 GTP-Binding ProteinsPrimary Cell CultureBiophysicsGTPaseBiochemistry03 medical and health sciencesUbiquitinGenes ReporterAutophagyHumansRNA Small InterferingMolecular BiologyGene knockdownbiologyProtein StabilityChemistryfungiAutophagyCell BiologyFibroblastsCell biologyLuminescent Proteins030104 developmental biologyProteostasisGene Expression Regulationrab GTP-Binding ProteinsProteolysisbiology.proteinCancer researchRabSignal transductionRAB18Signal TransductionBiochemical and Biophysical Research Communications
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