scholarly journals p38/MAPK is required for protein aggregate formation and removal by autophagy upon proteasome dysfunction

2022 ◽  
Vol 100 (S267) ◽  
Author(s):  
Ali Koskela ◽  
Johanna Ruuth ◽  
Szabolcs Felszeghy ◽  
Kai Kaarniranta
Keyword(s):  
P38 Mapk ◽  
Aggregate Formation ◽  
Protein Aggregate

scholarly journals Protein Aggregation is Associated with Acinetobacter baumannii Desiccation Tolerance

2020 ◽  
Vol 8 (3) ◽  
pp. 343 ◽  
Author(s):  
Xun Wang ◽  
Cody G. Cole ◽  
Cory D. DuPai ◽  
Bryan W. Davies
Keyword(s):  
Acinetobacter Baumannii ◽  
Desiccation Tolerance ◽  
Bacterial Pathogen ◽  
Protein Aggregates ◽  
Cellular Protein ◽  
Aggregate Formation ◽  
Growth Phases ◽  
Protein Aggregate ◽  
Factors Influencing ◽  
Cellular Aggregates

Desiccation tolerance has been implicated as an important characteristic that potentiates the spread of the bacterial pathogen Acinetobacter baumannii on dry surfaces. Here we explore several factors influencing desiccation survival of A. baumannii. At the macroscale level, we find that desiccation tolerance is influenced by cell density and growth phase. A transcriptome analysis indicates that desiccation represents a unique state for A. baumannii compared to commonly studied growth phases and strongly influences pathways responsible for proteostasis. Remarkably, we find that an increase in total cellular protein aggregates, which is often considered deleterious, correlates positively with the ability of A. baumannii to survive desiccation. We show that inducing protein aggregate formation prior to desiccation increases survival and, importantly, that proteins incorporated into cellular aggregates can retain activity. Our results suggest that protein aggregates may promote desiccation tolerance in A. baumannii through preserving and protecting proteins from damage during desiccation until rehydration occurs.

Whey protein aggregate formation during heating in the presence of κ-carrageenan

2009 ◽  
Vol 115 (4) ◽  
pp. 1479-1485 ◽  
Author(s):  
Kelly L. Flett ◽  
Milena Corredig
Keyword(s):  
Whey Protein ◽  
Aggregate Formation ◽  
Protein Aggregate

scholarly journals DRES-14. PROTEIN AGGREGATE FORMATION PREDICTS CLINICAL RESPONSES TO EGFR TKIs

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi78-vi78
Author(s):  
Pim French ◽  
Ya Gao ◽  
Maurice de Wit ◽  
Darlene Mercieca ◽  
Iris de Heer ◽  
...  
Keyword(s):  
Aggregate Formation ◽  
Protein Aggregate ◽  
Clinical Responses ◽  
Egfr Tkis

scholarly journals Ube2v1 Positively Regulates Protein Aggregation by Modulating Ubiquitin Proteasome System Performance Partially Through K63 Ubiquitination

2020 ◽  
Vol 126 (7) ◽  
pp. 907-922 ◽  
Author(s):  
Na Xu ◽  
James Gulick ◽  
Hanna Osinska ◽  
Yang Yu ◽  
Patrick M. McLendon ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
System Performance ◽  
Ubiquitin Proteasome System ◽  
Neonatal Rat ◽  
Autophagic Flux ◽  
Aggregate Formation ◽  
Protein Aggregate ◽  
Ventricular Cardiomyocytes ◽  
A Genome ◽  
Ubiquitin Proteasome

Rationale: Compromised protein quality control can result in proteotoxic intracellular protein aggregates in the heart, leading to cardiac disease and heart failure. Defining the participants and understanding the underlying mechanisms of cardiac protein aggregation is critical for seeking therapeutic targets. We identified Ube2v1 (ubiquitin-conjugating enzyme E2 variant 1) in a genome-wide screen designed to identify novel effectors of the aggregation process. However, its role in the cardiomyocyte is undefined. Objective: To assess whether Ube2v1 regulates the protein aggregation caused by cardiomyocyte expression of a mutant αB crystallin (CryAB R120G ) and identify how Ube2v1 exerts its effect. Methods and Results: Neonatal rat ventricular cardiomyocytes were infected with adenoviruses expressing either wild-type CryAB (CryAB WT ) or CryAB R120G . Subsequently, loss- and gain-of-function experiments were performed. Ube2v1 knockdown decreased aggregate accumulation caused by CryAB R120G expression. Overexpressing Ube2v1 promoted aggregate formation in CryAB WT and CryAB R120G -expressing neonatal rat ventricular cardiomyocytes. Ubiquitin proteasome system performance was analyzed using a ubiquitin proteasome system reporter protein. Ube2v1 knockdown improved ubiquitin proteasome system performance and promoted the degradation of insoluble ubiquitinated proteins in CryAB R120G cardiomyocytes but did not alter autophagic flux. Lys (K) 63-linked ubiquitination modulated by Ube2v1 expression enhanced protein aggregation and contributed to Ube2v1’s function in regulating protein aggregate formation. Knocking out Ube2v1 exclusively in cardiomyocytes by using AAV9 (adeno-associated virus 9) to deliver multiplexed single guide RNAs against Ube2v1 in cardiac-specific Cas9 mice alleviated CryAB R120G -induced protein aggregation, improved cardiac function, and prolonged lifespan in vivo. Conclusions: Ube2v1 plays an important role in protein aggregate formation, partially by enhancing K63 ubiquitination during a proteotoxic stimulus. Inhibition of Ube2v1 decreases CryAB R120G -induced aggregate formation through enhanced ubiquitin proteasome system performance rather than autophagy and may provide a novel therapeutic target to treat cardiac proteinopathies.

scholarly journals Protein aggregate formation permits millennium-old brain preservation

2020 ◽  
Vol 17 (162) ◽  
pp. 20190775 ◽  
Author(s):  
Axel Petzold ◽  
Ching-Hua Lu ◽  
Mike Groves ◽  
Johan Gobom ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Human Brain ◽  
Protein Aggregates ◽  
Poor Quality ◽  
Mass Spectrometry Data ◽  
Aggregate Formation ◽  
Protein Aggregate ◽  
Brain Proteins ◽  
Human Proteins ◽  
Tissue Homogenates

Human proteins have not been reported to survive in free nature, at ambient temperature, for long periods. Particularly, the human brain rapidly dissolves after death due to auto-proteolysis and putrefaction. The here presented discovery of 2600-year-old brain proteins from a radiocarbon dated human brain provides new evidence for extraordinary long-term stability of non-amyloid protein aggregates. Immunoelectron microscopy confirmed the preservation of neurocytoarchitecture in the ancient brain, which appeared shrunken and compact compared to a modern brain. Resolution of intermediate filaments (IFs) from protein aggregates took 2–12 months. Immunoassays on micro-dissected brain tissue homogenates revealed the preservation of the known protein topography for grey and white matter for type III (glial fibrillary acidic protein, GFAP) and IV (neurofilaments, Nfs) IFs. Mass spectrometry data could be matched to a number of peptide sequences, notably for GFAP and Nfs. Preserved immunogenicity of the prehistoric human brain proteins was demonstrated by antibody generation (GFAP, Nfs, myelin basic protein). Unlike brain proteins, DNA was of poor quality preventing reliable sequencing. These long-term data from a unique ancient human brain demonstrate that aggregate formation permits for the preservation of brain proteins for millennia.

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