scholarly journals Proteomics of broad deubiquitylase inhibition unmasks redundant enzyme function to reveal substrates

2019 ◽  
Author(s):  
Valentina Rossio ◽  
Joao A. Paulo ◽  
Joel Chick ◽  
Bradley Brasher ◽  
Steven P. Gygi ◽  
...  
Keyword(s):  
Proteasomal Degradation ◽  
Evolutionary Conservation ◽  
New Approach ◽  
Egg Extract ◽  
Human Proteins ◽  
Control Stability ◽  
Free Ubiquitin ◽  
Comprehensive Characterization ◽  
Unique Ability

AbstractDeubiquitylating enzymes (DUBs) counteract ubiquitylation to control stability or activity of substrates. Identification of DUB substrates is challenging because multiple DUBs act on the same substrates, thwarting genetic approaches. Here, we circumvented redundancy by broadly inhibiting DUBs in Xenopus egg extract. DUB inhibition increases ubiquitylation of hundreds of proteins, depleting free ubiquitin without inducing widespread degradation. Restoring available ubiquitin led to proteasomal degradation of over thirty proteins, indicating that deubiquitylation is essential to maintain their stability. We confirmed their DUB-dependent stability with recombinant human proteins, demonstrating evolutionary conservation. We profiled the ability of DUBs to rescue protein stability, and found that USP7 has a unique ability to broadly antagonize proteasomal degradation. Together, we provide a comprehensive characterization of ubiquitin dynamics in the Xenopus system, identify new DUB substrates, and present a new approach to characterize physiological DUB specificity that overcomes challenges posed by DUB redundancy

scholarly journals Avoided motifs: short amino acid strings missing from protein datasets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Function ◽  
Large Protein ◽  
New Approach ◽  
Cellular Context ◽  
Human Proteins ◽  
Context Specific ◽  
Protein Datasets

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.

scholarly journals Sustainability Investigation of Vehicles’ CO2 Emission in Hungary

2021 ◽  
Vol 13 (15) ◽  
pp. 8237
Author(s):  
István Árpád ◽  
Judit T. Kiss ◽  
Gábor Bellér ◽  
Dénes Kocsis
Keyword(s):  
Energy Efficiency ◽  
Co2 Emissions ◽  
Energy Supply ◽  
Internal Combustion Engines ◽  
Combustion Engines ◽  
The European Union ◽  
New Approach ◽  
Technology System ◽  
Low Co2

The regulation of vehicular CO2 emissions determines the permissible emissions of vehicles in units of g CO2/km. However, these values only partially provide adequate information because they characterize only the vehicle but not the emission of the associated energy supply technology system. The energy needed for the motion of vehicles is generated in several ways by the energy industry, depending on how the vehicles are driven. These methods of energy generation consist of different series of energy source conversions, where the last technological step is the vehicle itself, and the result is the motion. In addition, sustainability characterization of vehicles cannot be determined by the vehicle’s CO2 emissions alone because it is a more complex notion. The new approach investigates the entire energy technology system associated with the generation of motion, which of course includes the vehicle. The total CO2 emissions and the resulting energy efficiency have been determined. For this, it was necessary to systematize (collect) the energy supply technology lines of the vehicles. The emission results are not given in g CO2/km but in g CO2/J, which is defined in the paper. This new method is complementary to the European Union regulative one, but it allows more complex evaluations of sustainability. The calculations were performed based on Hungarian data. Finally, using the resulting energy efficiency values, the emission results were evaluated by constructing a sustainability matrix similar to the risk matrix. If only the vehicle is investigated, low CO2 emissions can be achieved with vehicles using internal combustion engines. However, taking into consideration present technologies, in terms of sustainability, the spread of electric-only vehicles using renewable energies can result in improvement in the future. This proposal was supported by the combined analysis of the energy-specific CO2 emissions and the energy efficiency of vehicles with different power-driven systems.

scholarly journals An Intrinsic Characterization of Five Points in a CAT(0) Space

2020 ◽  
Vol 8 (1) ◽  
pp. 114-165
Author(s):  
Tetsu Toyoda
Keyword(s):  
Metric Space ◽  
Isometric Embedding ◽  
Metric Spaces ◽  
Necessary Conditions ◽  
New Approach ◽  
Intrinsic Characterization ◽  
New Family

AbstractGromov (2001) and Sturm (2003) proved that any four points in a CAT(0) space satisfy a certain family of inequalities. We call those inequalities the ⊠-inequalities, following the notation used by Gromov. In this paper, we prove that a metric space X containing at most five points admits an isometric embedding into a CAT(0) space if and only if any four points in X satisfy the ⊠-inequalities. To prove this, we introduce a new family of necessary conditions for a metric space to admit an isometric embedding into a CAT(0) space by modifying and generalizing Gromov’s cycle conditions. Furthermore, we prove that if a metric space satisfies all those necessary conditions, then it admits an isometric embedding into a CAT(0) space. This work presents a new approach to characterizing those metric spaces that admit an isometric embedding into a CAT(0) space.

scholarly journals Comprehensive characterization of the genomic alterations in human gastric cancer

2014 ◽  
Vol 137 (1) ◽  
pp. 86-95 ◽  
Author(s):  
Juan Cui ◽  
Yanbin Yin ◽  
Qin Ma ◽  
Guoqing Wang ◽  
Victor Olman ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Human Gastric Cancer ◽  
Genomic Alterations ◽  
Comprehensive Characterization
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