Philipp Trepte

HAP40 functions as a proteostasis regulator by controlling huntingtin interactions and its release into the extracellular space

Eduardo Silva Ramos, Annett Boeddrich, Christian Haenig, Philipp Trepte et autres

Abstract Huntingtin-associated protein 40 (HAP40) forms a stable protein complex with huntingtin (HTT). Its cellular function and how HAP40 loss influences mutant HTT (mHTT) abundance and pathobiology are currently unclear. Here, using diverse cellular models and OMICs methods, we demonstrate that HAP40 …

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AI-guided pipeline for protein–protein interaction drug discovery identifies a SARS-CoV-2 inhibitor

Philipp Trepte, Christopher Secker, Julien Olivet, Jérémy Blavier et autres

Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and …

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AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor

Philipp Trepte, Christopher Secker, Simona Kostova, Sibusiso B. Maseko et autres

Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and …

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Integrated transcriptome and proteome analysis reveals posttranscriptional regulation of ribosomal genes in human brain organoids

Jaydeep Sidhaye, Philipp Trepte, Natalie Sepke, Maria Novatchkova et autres

During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the posttranscriptional control of gene expression and protein …

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Author response: Integrated transcriptome and proteome analysis reveals posttranscriptional regulation of ribosomal genes in human brain organoids

Jaydeep Sidhaye, Philipp Trepte, Natalie Sepke, Maria Novatchkova et autres

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Integrated transcriptome and proteome analysis in human brain organoids reveals posttranscriptional regulation of ribosomal genes

Jaydeep Sidhaye, Philipp Trepte, Natalie Sepke, Maria Novatchkova et autres

During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein …

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CellFIE: CRISPR- and Cell Fusion-based Two-hybrid Interaction Mapping of Endogenous Proteins

Christopher Secker, Simona Kostova, Hannah Niederlechner, Stephanie Beetz et autres

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A quantitative mapping approach to identify direct interactions within complexomes

Philipp Trepte, Christopher Secker, Soon Gang Choi, Julien Olivet et autres

ABSTRACT Complementary methods are required to fully characterize all protein complexes, or the complexome, of a cell. Affinity purification coupled to mass-spectrometry (AP-MS) can identify the composition of complexes at proteome-scale. However, information on direct contacts between subunits is often lacking. In …

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Polyglutamine-Rich Suppressors of Huntingtin Toxicity Act Upstream of Hsp70 and Sti1 in Spatial Quality Control of Amyloid-Like Proteins

Douglas Cyr, Philipp Trepte, Hong Yu Ren, Katie J. Wolfe

Protein conformational maladies such as Huntington Disease are characterized by accumulation of intracellular and extracellular protein inclusions containing amyloid-like proteins. There is an inverse correlation between proteotoxicity and aggregation, so facilitated protein aggregation appears cytoprotective. To define mechanisms for protective protein aggregation, …

The Hsp70/90 cochaperone, Sti1, suppresses proteotoxicity by regulating spatial quality control of amyloid-like proteins

Philipp Trepte, Hong Yu Rena, Douglas Cyr, Katie J. Wolfe

Escape of aberrant proteins from protein quality control leads to accumulation of toxic protein species. Sti1 interacts with Hsp70 to mediate spatial PQC of amyloid-like proteins by regulating their distribution in different intracellular protein-handling depots. Sti1 suppresses proteotoxicity by targeting amyloid-like proteins …

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Maximizing binary interactome mapping with a minimal number of assays

Soon Gang Choi, Julien Olivet, Patricia Cassonnet, Pierre‐Olivier Vidalain et autres

Complementary assays are required to comprehensively map complex biological entities such as genomes, proteomes and interactome networks. However, how various assays can be optimally combined to approach completeness while maintaining high precision often remains unclear. Here, we propose a framework for binary …

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The pathobiology of perturbed mutant huntingtin protein–protein interactions in Huntington's disease

Erich E. Wanker, Anne Ast, Franziska Schindler, Philipp Trepte et autres

Mutations are at the root of many human diseases. Still, we largely do not exactly understand how they trigger pathogenesis. One, more recent, hypothesis has been that they comprehensively perturb protein-protein interaction (PPI) networks and significantly alter key biological processes. Under this …

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