0000000000925814

AUTHOR

Gunnar Dittmar

0000-0003-3647-8623

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]
researchProduct

Deregulated Splicing Is a Major Mechanism of RNA-Induced Toxicity in Huntington's Disease.

2019

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant…

congenital hereditary and neonatal diseases and abnormalitiesSpliceosomeHuntingtinRNA SplicingMutantRNA-binding proteinRNA-binding proteinsBiologygenetics [Huntington Disease]Structural Biologymental disordersmedicineAnimalsHumansddc:610genetics [RNA]Molecular BiologyGeneHuntingtin Proteingenetics [Spliceosomes]CAG repeat RNANeurodegenerationneurodegenerationRNAgenetics [Huntingtin Protein]medicine.diseasenervous system diseasesCell biologypolyglutamine diseaseHuntington Diseasenervous systemCardiovascular and Metabolic DiseasesRNA splicingSpliceosomesgenetics [RNA Splicing]RNATechnology PlatformsspliceosomeJournal of molecular biology
researchProduct