scholarly journals Biological Functionalities of Transglutaminase 2 and the Possibility of Its Compensation by Other Members of the Transglutaminase Family

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Benedict Onyekachi Odii ◽  
Peter Coussons
Keyword(s):  
Substrate Specificity ◽  
Posttranslational Modification ◽  
Transglutaminase 2 ◽  
Extracellular Proteins ◽  
Gene Products ◽  
Biological Functions ◽  
Matrix Stabilization ◽  
Wide Range ◽  
Cell Growth And Differentiation ◽  
Cellular Development

Transglutaminase 2 (TG2) is the most widely distributed and most abundantly expressed member of the transglutaminase family of enzymes, a group of intracellular and extracellular proteins that catalyze the Ca2+-dependent posttranslational modification of proteins. It is a unique member of the transglutaminase family owing to its specialized biochemical, structural and functional elements, ubiquitous tissue distribution and subcellular localization, and substrate specificity. The broad substrate specificity of TG2 and its flexible interaction with numerous other gene products may account for its multiple biological functions. In addition to the classic Ca2+-dependent transamidation of proteins, which is a hallmark of transglutaminase enzymes, additional Ca2+-independent enzymatic and nonenzymatic activities of TG2 have been identified. Many such activities have been directly or indirectly implicated in diverse cellular physiological events, including cell growth and differentiation, cell adhesion and morphology, extracellular matrix stabilization, wound healing, cellular development, receptor-mediated endocytosis, apoptosis, and disease pathology. Given the wide range of activities of the transglutaminase gene family it has been suggested that, in the absence of active versions of TG2, its function could be compensated for by other members of the transglutaminase family. It is in the light of this assertion that we review, herein, TG2 activities and the possibilities and premises for compensation for its absence.

Structure and properties of the Ca2+-binding CUB domain, a widespread ligand-recognition unit involved in major biological functions

2011 ◽  
Vol 439 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Christine Gaboriaud ◽  
Lynn Gregory-Pauron ◽  
Florence Teillet ◽  
Nicole M. Thielens ◽  
Isabelle Bally ◽  
...  
Keyword(s):  
Binding Site ◽  
Protein Interactions ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Extracellular Proteins ◽  
Present Review ◽  
Biological Functions ◽  
Protein Motifs ◽  
Wide Range ◽  
Cub Domain

CUB domains are 110-residue protein motifs exhibiting a β-sandwich fold and mediating protein–protein interactions in various extracellular proteins. Recent X-ray structural and mutagenesis studies have led to the identification of a particular CUB domain subset, cbCUB (Ca2+-binding CUB domain). Unlike other CUB domains, these harbour a homologous Ca2+-binding site that underlies a conserved binding site mediating ionic interaction between two of the three conserved acidic Ca2+ ligands and a basic (lysine or arginine) residue of a protein ligand, similar to the interactions mediated by the low-density lipoprotein receptor family. cbCUB-mediated protein–ligand interactions usually involve multipoint attachment through several cbCUBs, resulting in high-affinity binding through avidity, despite the low affinity of individual interactions. The aim of the present review is to summarize our current knowledge about the structure and functions of cbCUBs, which represent the majority of the known CUB repertoire and are involved in a variety of major biological functions, including immunity and development, as well as in various cancer types. Examples discussed in the present review include a wide range of soluble and membrane-associated human proteins, as well as some archaeal and invertebrate proteins. The fact that these otherwise unrelated proteins share a common Ca2+-dependent ligand-binding ability suggests a mechanism inheri-ted from very primitive ancestors. The information provided in the present review should stimulate further investigations on the crucial interactions mediated by cbCUB-containing proteins.

scholarly journals UFMylation regulates translational homeostasis and cell cycle progression

2020 ◽  
Author(s):  
Igor A. Gak ◽  
Djordje Vasiljevic ◽  
Thomas Zerjatke ◽  
Lu Yu ◽  
Mario Brosch ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Translation Initiation ◽  
Posttranslational Modification ◽  
Cell Cycle Progression ◽  
Ribosome Profiling ◽  
Biological Functions ◽  
Initiation Complex ◽  
Cycle Progression ◽  
Cellular Targets ◽  
Global Translation

SummaryUFMylation, the posttranslational modification of proteins with ubiquitin fold modifier 1 (UFM1) is essential for metazoan life and is associated with multiple human diseases. Although UFMylation has been linked to endoplasmic reticulum (ER) stress, its biological functions and relevant cellular targets beyond the ER are obscure. Here, we show that UFMylation directly controls translation and cell division in a manner otherwise known for cellular homeostasis-sensing pathways such as mTOR. By combining cell cycle analyses, mass spectrometry and ribosome profiling we demonstrate that UFMylation is required for eIF4F translation initiation complex assembly and recruitment of the ribosome. Interference with UFMylation shuts down global translation, which is sensed by cyclin D1 and halts the cell cycle independently of integrated stress response signalling. Our findings establish UFMylation as a key regulator of translation and uncover a pathway that couples translational homeostasis to cell cycle progression via a ubiquitin-like modification.

scholarly journals Deep6mA: A deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species

2021 ◽  
Vol 17 (2) ◽  
pp. e1008767
Author(s):  
Zutan Li ◽  
Hangjin Jiang ◽  
Lingpeng Kong ◽  
Yuanyuan Chen ◽  
Kun Lang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Prediction Accuracy ◽  
Cross Validation ◽  
Biological Processes ◽  
Biological Functions ◽  
Learning Framework ◽  
Wide Range ◽  
Genomic Scale ◽  
Downstream Gene Expression ◽  
Fold Cross Validation

N6-methyladenine (6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for under-standing of 6mA’s biological functions. However, the existing experimental techniques for detecting 6mA sites are cost-ineffective, which implies the great need of developing new computational methods for this problem. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species: Arabidopsis thaliana, Fragaria vesca and Rosa chinensis with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression.

Characterization of proteins with Siaα2-3/6Gal-linked glycans from bovine milk and role of their glycans against influenza A virus

2018 ◽  
Vol 9 (10) ◽  
pp. 5198-5208 ◽  
Author(s):  
Hanjie Yu ◽  
Yaogang Zhong ◽  
Zhiwei Zhang ◽  
Xiawei Liu ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Bovine Milk ◽  
Milk Proteins ◽  
Biological Functions ◽  
Wide Range ◽  
Range Of Functions ◽  
Bovine Milk Proteins

The bovine milk proteins have a wide range of functions, but the role of the attached glycans in their biological functions has not been fully understood yet.

scholarly journals Influence of Gemini Surfactants on Biochemical Profile and Ultrastructure of Aspergillus brasiliensis

2019 ◽  
Vol 9 (2) ◽  
pp. 245 ◽  
Author(s):  
Anna Koziróg ◽  
Anna Otlewska ◽  
Magdalena Gapińska ◽  
Sylwia Michlewska
Keyword(s):  
Gemini Surfactants ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Control Sample ◽  
Extracellular Proteins ◽  
Practical Applications ◽  
Aspergillus Brasiliensis ◽  
Cationic Gemini Surfactants ◽  
Wide Range ◽  
Cationic Compounds

In this study, we investigated the activities of hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C6), pentamethylene-1,5-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C5), and their two neutral analogues: hexamethylene-1,6-bis-(N-methyl-N-dodecylamine) (A6) and pentamethylene-1,5-bis-(N-methyl-N-dodecylamine) (A5) at concentrations of ½ MIC, MIC, and 2 MIC (minimal inhibitory concentration) against hyphal forms of Aspergillus brasiliensis ATCC 16404. Enzymatic profiles were determined using the API-ZYM system. Extracellular proteins were extracted from the mycelia and analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The ultrastructure was evaluated using a transmission electron microscope (TEM). Both groups of surfactants caused changes in the enzyme profiles. Larger changes in the number and concentration of enzymes were noted after the action of non-ionic gemini surfactants, which may have been due to the 100× higher concentration of neutral compounds. Larger differences between the protein profiles of the control sample and the biocide samples were observed following the use of cationic compounds. On the basis of TEM analyses, we found that, with increasing concentrations of compound C6, the mycelium cells gradually degraded. After treatment at 2 MIC, only membranous structures, multiform bodies, and dense electron pellets remained. Based on these results, we concluded that cationic gemini surfactants, in comparison with their non-ionic analogues, could have a wide range of practical applications as active compounds.

scholarly journals LncExpDB: an expression database of human long non-coding RNAs

2020 ◽  
Vol 49 (D1) ◽  
pp. D962-D968 ◽  
Author(s):  
Zhao Li ◽  
Lin Liu ◽  
Shuai Jiang ◽  
Qianpeng Li ◽  
Changrui Feng ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Biological Functions ◽  
Protein Coding ◽  
Web Interfaces ◽  
Functional Studies ◽  
Protein Coding Genes ◽  
Genes Expression ◽  
Wide Range ◽  
Non Coding Rnas ◽  
User Friendly

Abstract Expression profiles of long non-coding RNAs (lncRNAs) across diverse biological conditions provide significant insights into their biological functions, interacting targets as well as transcriptional reliability. However, there lacks a comprehensive resource that systematically characterizes the expression landscape of human lncRNAs by integrating their expression profiles across a wide range of biological conditions. Here, we present LncExpDB (https://bigd.big.ac.cn/lncexpdb), an expression database of human lncRNAs that is devoted to providing comprehensive expression profiles of lncRNA genes, exploring their expression features and capacities, identifying featured genes with potentially important functions, and building interactions with protein-coding genes across various biological contexts/conditions. Based on comprehensive integration and stringent curation, LncExpDB currently houses expression profiles of 101 293 high-quality human lncRNA genes derived from 1977 samples of 337 biological conditions across nine biological contexts. Consequently, LncExpDB estimates lncRNA genes’ expression reliability and capacities, identifies 25 191 featured genes, and further obtains 28 443 865 lncRNA-mRNA interactions. Moreover, user-friendly web interfaces enable interactive visualization of expression profiles across various conditions and easy exploration of featured lncRNAs and their interacting partners in specific contexts. Collectively, LncExpDB features comprehensive integration and curation of lncRNA expression profiles and thus will serve as a fundamental resource for functional studies on human lncRNAs.

scholarly journals The N-glycans of lactoferrin: More than just a sweet decoration.

2020 ◽  
Author(s):  
Kristina Zlatina ◽  
Sebastian Peter Galuska
Keyword(s):  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Extracellular Proteins ◽  
Bovine Lactoferrin ◽  
Carrier Protein ◽  
Therapeutic Approaches ◽  
Heterogeneous Effects ◽  
Potential Impact ◽  
Sugar Chains ◽  
Different Origins

Nearly all extracellular proteins undergo posttranslational modification with sugar chains during their transit through the endoplasmic reticulum and the Golgi apparatus. These “sweet” modifications not only influence the activity of its carrier protein, but they themselves often have bioactivity, independent of the carrier function. Lactoferrin belongs to the group of glycoproteins and is modified with several different N-glycans. This review summarizes several studies dealing with the diverse glycosylation patterns of lactoferrin from different origins and the potential impact of these posttranslational modifications on the functionality of lactoferrin. A special emphasis is placed on the differences between human and bovine lactoferrin, since the latter form is often selected for the development of novel therapeutic approaches in humans. For this reason, the potential impact of the bovine-specific glycosylation patterns on the observed heterogeneous effects of lactoferrin in humans is discussed within this review.

scholarly journals Evidence for a link between IGF-I and cancer

2004 ◽  
pp. S17-S22 ◽  
Author(s):  
PJ Jenkins ◽  
SA Bustin
Keyword(s):  
Cancer Risk ◽  
Molecular Mechanisms ◽  
Normal Function ◽  
The Body ◽  
Signalling Pathways ◽  
Biological Functions ◽  
Related Factors ◽  
Wide Range ◽  
Igf I ◽  
Inappropriate Expression

Cancer risk is determined by a combination of environmental factors and genetic predisposition. Recent evidence suggests that dietary and related factors such as physical activity and body size may influence cancer risk through their effects on the serum concentration of IGF-I and its binding proteins. The growth hormone (GH)/IGF-I axis is involved in both human development as well as the maintenance of normal function and homeostasis in most cells of the body. In addition to their classical role as endocrine hormones, its members regulate a wide range of biological functions such as cell proliferation, differentiation and apoptosis through paracrine and autocrine mechanisms. During cancer development this complex network regulating tissue homeostasis breaks down, with inappropriate expression of the GH/IGF-I axis making an important contribution. The increased understanding of the molecular mechanisms and signalling pathways regulated by the GH/IGF-I axis has started to provide significant insights into the aetiology, prevention and therapy for a number of common cancers.

scholarly journals The Three Clades of the Telomere-AssociatedTLOGene Family of Candida albicans Have Different Splicing, Localization, and Expression Features

2012 ◽  
Vol 11 (10) ◽  
pp. 1268-1275 ◽  
Author(s):  
Matthew Z. Anderson ◽  
Joshua A. Baller ◽  
Keely Dulmage ◽  
Lauren Wigen ◽  
Judith Berman
Keyword(s):  
Candida Albicans ◽  
Gene Family ◽  
Transcription Regulation ◽  
Family Members ◽  
Gene Products ◽  
Content Type ◽  
Human Host ◽  
Wide Range ◽  
N Terminus

ABSTRACTCandida albicansgrows within a wide range of host niches, and this adaptability enhances its success as a commensal and as a pathogen. The telomere-associatedTLOgene family underwent a recent expansion from one or two copies in other CUG clade members to 14 expressed copies inC. albicans. This correlates with increased virulence and clinical prevalence relative to those of otherCandidaclade species. The 14 expressedTLOgene family members have a conserved Med2 domain at the N terminus, suggesting a role in general transcription. The C-terminal half is more divergent, distinguishing three clades: clade α and clade β have no introns and encode proteins that localize primarily to the nucleus; clade γ sometimes undergoes splicing, and the gene products localize within the mitochondria as well as the nuclei. Additionally,TLOα genes are generally expressed at much higher levels than areTLOγ genes. We propose that expansion of theTLOgene family and the predicted role of Tlo proteins in transcription regulation provideC. albicanswith the ability to adapt rapidly to the broad range of different environmental niches within the human host.

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