scholarly journals The role of spartin and its novel ubiquitin binding region in DALIS occurrence

2014 ◽  
Vol 25 (8) ◽  
pp. 1355-1365 ◽  
Author(s):  
Amelia B. Karlsson ◽  
Jacqueline Washington ◽  
Valentina Dimitrova ◽  
Christopher Hooper ◽  
Alexander Shekhtman ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Resonance Spectroscopy ◽  
Spastic Paraplegia ◽  
Binding Region ◽  
Hairpin Rna ◽  
Multifunctional Protein ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Key Residues

Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin's UBR and defined the UBR's amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin's role in DALIS formation depends on key residues within its UBR.

scholarly journals Role of the ubiquitin-binding domain of Polη in Rad18-independent translesion DNA synthesis in human cell extracts

2010 ◽  
Vol 38 (19) ◽  
pp. 6456-6465 ◽  
Author(s):  
Valérie Schmutz ◽  
Régine Janel-Bintz ◽  
Jérôme Wagner ◽  
Denis Biard ◽  
Naoko Shiomi ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Human Cell ◽  
Binding Domain ◽  
Translesion Dna Synthesis ◽  
Cell Extracts ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Translesion Dna

scholarly journals Selective Autophagy by Close Encounters of the Ubiquitin Kind

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2349 ◽  
Author(s):  
Anna Vainshtein ◽  
Paolo Grumati
Keyword(s):  
Protein Aggregates ◽  
Degradation Process ◽  
Eukaryotic Cells ◽  
Post Translational Modifications ◽  
Selective Autophagy ◽  
Close Encounters ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Cellular Turnover

Autophagy, a bulk degradation process within eukaryotic cells, is responsible for cellular turnover and nutrient liberation during starvation. Increasing evidence indicate that this process can be extremely discerning. Selective autophagy segregates and eliminates protein aggregates, damaged organelles, and invading organisms. The specificity of this process is largely mediated by post-translational modifications (PTMs), which are recognized by autophagy receptors. These receptors grant autophagy surgical precision in cargo selection, where only tagged substrates are engulfed within autophagosomes and delivered to the lysosome for proteolytic breakdown. A growing number of selective autophagy receptors have emerged including p62, NBR1, OPTN, NDP52, TAX1BP1, TOLLIP, and more continue to be uncovered. The most well-documented PTM is ubiquitination and selective autophagy receptors are equipped with a ubiquitin binding domain and an LC3 interacting region which allows them to physically bridge cargo to autophagosomes. Here, we review the role of ubiquitin and ubiquitin-like post-translational modifications in various types of selective autophagy.

scholarly journals Specificity in Ubiquitination Triggered by Virus Infection

2020 ◽  
Vol 21 (11) ◽  
pp. 4088 ◽  
Author(s):  
Haidong Gu ◽  
Behdokht Jan Fada
Keyword(s):  
Host Interactions ◽  
Ubiquitinated Proteins ◽  
Virus Life Cycle ◽  
Ubiquitin System ◽  
Ubiquitin Binding ◽  
Lysine Residues ◽  
Ubiquitin Binding Domain ◽  
Ubiquitin Moiety ◽  
The Rich

Ubiquitination is a prominent posttranslational modification, in which the ubiquitin moiety is covalently attached to a target protein to influence protein stability, interaction partner and biological function. All seven lysine residues of ubiquitin, along with the N-terminal methionine, can each serve as a substrate for further ubiquitination, which effectuates a diverse combination of mono- or poly-ubiquitinated proteins with linear or branched ubiquitin chains. The intricately composed ubiquitin codes are then recognized by a large variety of ubiquitin binding domain (UBD)-containing proteins to participate in the regulation of various pathways to modulate the cell behavior. Viruses, as obligate parasites, involve many aspects of the cell pathways to overcome host defenses and subjugate cellular machineries. In the virus-host interactions, both the virus and the host tap into the rich source of versatile ubiquitination code in order to compete, combat, and co-evolve. Here, we review the recent literature to discuss the role of ubiquitin system as the infection progresses in virus life cycle and the importance of ubiquitin specificity in the regulation of virus-host relation.

scholarly journals A Novel Epigenetic Regulator ZRF1: Insight into Its Functions in Plants

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1245
Author(s):  
Jing Feng ◽  
Yahui Gao ◽  
Kun Wang ◽  
Mingguo Jiang
Keyword(s):  
Target Genes ◽  
Higher Plants ◽  
Research Progress ◽  
Related Factor ◽  
Histone H2a ◽  
Epigenetic Regulator ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Insight Into

Recently, Zuotin-related factor 1 (ZRF1), an epigenetic regulator, was found to be involved in transcriptional regulation. In animals and humans, ZRF1 specifically binds to monoubiquitinated histone H2A through a ubiquitin-binding domain and derepresses Polycomb target genes at the beginning of cellular differentiation. In addition, ZRF1 can work as a tumor suppressor. According to bioinformatics analysis, ZRF1 homologs are widely found in plants. However, the current studies on ZRF1 in higher plants are limited and few in-depth studies of its functions have been reported. In this review, we aim to summarize the key role of AtZRF1a/b in Arabidopsis thaliana growth and development, as well as the research progress in this field in recent years.

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

scholarly journals DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Monica del C. Gomez-Alonso ◽  
Anja Kretschmer ◽  
Rory Wilson ◽  
Liliane Pfeiffer ◽  
Ville Karhunen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Population Based ◽  
Total Serum ◽  
Resonance Spectroscopy ◽  
Metabolic Disturbances ◽  
Cpg Sites ◽  
Gene Transcripts

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.

scholarly journals Mouse models for hereditary spastic paraplegia uncover a role of PI4K2A in autophagic lysosome reformation

Autophagy ◽  
2021 ◽  
pp. 1-17
Author(s):  
Mukhran Khundadze ◽  
Federico Ribaudo ◽  
Adeela Hussain ◽  
Henry Stahlberg ◽  
Nahal Brocke-Ahmadinejad ◽  
...  
Keyword(s):  
Mouse Models ◽  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia

scholarly journals Environmentally persistent free radicals are ubiquitous in wildfire charcoals and remain stable for years

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Gabriel Sigmund ◽  
Cristina Santín ◽  
Marc Pignitter ◽  
Nathalie Tepe ◽  
Stefan H. Doerr ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Reactive Oxygen ◽  
Resonance Spectroscopy ◽  
Oxygen Species ◽  
Pyrogenic Carbon ◽  
Spin Resonance ◽  
Long Time ◽  
High Concentrations

AbstractGlobally landscape fires produce about 256 Tg of pyrogenic carbon or charcoal each year. The role of charcoal as a source of environmentally persistent free radicals, which are precursors of potentially harmful reactive oxygen species, is poorly constrained. Here, we analyse 60 charcoal samples collected from 10 wildfires, that include crown as well as surface fires in forest, shrubland and grassland spanning different boreal, temperate, subtropical and tropical climate. Using electron spin resonance spectroscopy, we measure high concentrations of environmentally persistent free radicals in charcoal samples, much higher than those found in soils. Concentrations increased with degree of carbonization and woody fuels favoured higher concentrations. Moreover, environmentally persistent free radicals remained stable for an unexpectedly long time of at least 5 years. We suggest that wildfire charcoal is an important global source of environmentally persistent free radicals, and therefore potentially of harmful reactive oxygen species.

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