scholarly journals Functional Proteomic Analysis of Human Nucleolus

2002 ◽  
Vol 13 (11) ◽  
pp. 4100-4109 ◽  
Author(s):  
Alexander Scherl ◽  
Yohann Couté ◽  
Catherine Déon ◽  
Aleth Callé ◽  
Karine Kindbeiter ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Convincing Evidence ◽  
Biological Processes ◽  
Functional Classification ◽  
Control Of Gene Expression ◽  
Nucleolar Proteins ◽  
Nuclear Domain

The notion of a “plurifunctional” nucleolus is now well established. However, molecular mechanisms underlying the biological processes occurring within this nuclear domain remain only partially understood. As a first step in elucidating these mechanisms we have carried out a proteomic analysis to draw up a list of proteins present within nucleoli of HeLa cells. This analysis allowed the identification of 213 different nucleolar proteins. This catalog complements that of the 271 proteins obtained recently by others, giving a total of ∼350 different nucleolar proteins. Functional classification of these proteins allowed outlining several biological processes taking place within nucleoli. Bioinformatic analyses permitted the assignment of hypothetical functions for 43 proteins for which no functional information is available. Notably, a role in ribosome biogenesis was proposed for 31 proteins. More generally, this functional classification reinforces the plurifunctional nature of nucleoli and provides convincing evidence that nucleoli may play a central role in the control of gene expression. Finally, this analysis supports the recent demonstration of a coupling of transcription and translation in higher eukaryotes.

scholarly journals Functional Proteomics of Regulatory and Epigenetic Signaling in Normal and Malignant Hematopoiesis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4972-4972 ◽  
Author(s):  
Paolo Cifani ◽  
Mojdeh Shakiba ◽  
Fiona Brown ◽  
Avantika Dhabaria ◽  
Daniel E. Bauer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Synthetic Peptide ◽  
High Efficiency ◽  
Limit Of Detection ◽  
Functional Proteomics ◽  
Functional Classification ◽  
Limits Of Detection ◽  
Control Of Gene Expression ◽  
Enhancer Factor

Abstract Post-translational modifications of proteins are increasingly recognized as key regulators of functional complexes assembly and cellular enzymes activity, processes that control both normal and aberrant cell growth and development. To enable comprehensive, sensitive and quantitative analysis of these processes, we adapted recently developed high-efficiency nanoscale multidimensional liquid chromatography with high-resolution Orbitrap mass spectrometry. Termed accumulated ion monitoring (AIM), this mass spectrometry method achieved nearly 7 orders of magnitude of quantitative accuracy and absolute limit of detection of 600 molecules per scan, enabling the study of rare cell populations (Fig. 1). We leveraged AIM mass spectrometry to develop a panel of 1583 synthetic reference peptides, based on global and published proteomics maps of normal human and leukemia cells. This Quantitative Cell Proteomics Atlas (QCPA) profiles 384 key effectors of cell surface signaling, proliferation, quiescence, stress response, and epigenetic control of gene expression (Fig. 2). QCPA enables unprecedented accuracy and sensitivity for the functional analysis of rare cells, with focus on protein regulation via phosphorylation, acetylation and methylation, as well as on concentration (http://alexkentsis.net/qcpa). By using functional proteomics profiling of primary human CD34+ and acute myeloid leukemia (AML) cells, we identify new pathways controlling erythrocyte differentiation and AML therapy resistance, as facilitated by a newly developed program ProteoModlR (http://github.com/kentsisresearchgroup/ProteoModlR). AIM mass spectrometry and QCPA functional proteomics are rapidly adaptable and generalizable tools for the investigation of regulatory and epigenetic signaling in normal and diseased cells. Figure 1. Limits of detection and quantitation for a serially diluted synthetic peptide from human Myocyte-specific Enhancer Factor 2C. Figure 1. Limits of detection and quantitation for a serially diluted synthetic peptide from human Myocyte-specific Enhancer Factor 2C. Figure 2. Functional classification of proteins included in the QCPA. Figure 2. Functional classification of proteins included in the QCPA. Disclosures Bauer: Editas Medicine: Consultancy; Biogen: Research Funding.

scholarly journals Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1597
Author(s):  
Olga V. Iarovaia ◽  
Elena S. Ioudinkova ◽  
Artem K. Velichko ◽  
Sergey V. Razin
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Viral Infection ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Infection Process ◽  
Regulatory Pathways ◽  
Nucleolar Proteins

Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection.

scholarly journals Comparative proteomic analysis of the sweetpotato provides insights into response mechanisms to Fusarium oxysporum f. sp. batatas

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
ShiQiang Lin ◽  
ZhiJian Yang ◽  
BiFang Huang ◽  
ChuYun Bi ◽  
XiaoFang Huang ◽  
...  
Keyword(s):  
Fusarium Oxysporum ◽  
Proteomic Analysis ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Defense Responses ◽  
Biological Processes ◽  
Go Annotation ◽  
Parallel Reaction Monitoring ◽  
Annotation Information ◽  
Insight Into

AbstractThe Fusarium wilt disease caused by Fusarium oxysporum f. sp. batatas (Fob) is one of the devastating diseases of sweetpotato. However, the molecular mechanisms of sweetpotato response to Fob is poorly understood. In the present study, comparative quantitative proteomic analysis was conducted to investigate the defense mechanisms involved. Two sweetpotato cultivars with differential Fob infection responses were inoculated with Fob spore suspensions and quantitatively analyzed by Tandem Mass Tags (TMT). 2267 proteins were identified and 1897 of them were quantified. There were 817 proteins with quantitative ratios of 1.2-fold change between Fob-inoculated and mock-treated samples. Further, nine differentially expressed proteins were validated by Parallel Reaction Monitoring (PRM). According to Gene Ontology (GO) annotation information, the proteins functioned in molecular metabolism, cellular component formation, and biological processes. Interestingly, the results showed that sweetpotato resistant response to Fob infection included many proteins associated with signaling transduction, plant resistance, chitinase and subtilisin-like protease. The functions and possible roles of those proteins were discussed. The results provides first insight into molecular mechanisms involved in sweetpotato defense responses to Fob.

scholarly journals miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy

2020 ◽  
Vol 14 (12) ◽  
pp. e0008889
Author(s):  
Laurie Laugier ◽  
Ludmila Rodrigues Pinto Ferreira ◽  
Frederico Moraes Ferreira ◽  
Sandrine Cabantous ◽  
Amanda Farage Frade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chagas Disease ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Heart Tissue ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Control Of Gene Expression ◽  
Network Analyses ◽  
Chronic Myocarditis

Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.

Contribution of microarrays of gene expression (MAGE) to the definition of PET/CT as a qualified biomarker of early response in metastatic patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11573-11573
Author(s):  
Manuel Sureda ◽  
Aurora Crespo-Jara ◽  
Ramon Gonzalez Manzano ◽  
Maria del Carmen Redal ◽  
Francisco Javier Garcia-Cases ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fdg Pet ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Gene Expression Signature ◽  
Early Response ◽  
Biological Processes ◽  
Microarray Gene Expression ◽  
Fdg Uptake ◽  
Pet Ct

11573 Background: Proliferating cancer cells consume elevated quantity of glucose, converted into lactate regardless the presence of oxygen (Warburg effect). This effect has been useful for imaging metabolically active tumors with FDG-PET, although its use in early response is controversial. Molecular mechanisms of FDG uptake are not fully understood. We have used MAGE to determine the most relevant genes involved in FDG uptake. Methods: Fresh-frozen tumor biopsies and quantitative basal FDG-PET/CT were obtained from metastatic lesions in cancer patients. Total tumor RNA was hybridized to a whole human genome oligonucleotide microarray. Gene expression signature-based prediction, using the most relevant genes involved in FDG uptake measured by SUV, was finally determined by Partial Least Squares (PLS). The interpretation of biological phenomena (IBP) derived from the selected genes was made by means of different public statistical bioinformatics resources. Results: 71 patients with different histological diagnosis were included in the training cohort and 13 in the validation one. 909 probes correlated significantly with SUV: 333 positively and 576 negatively. A predictive signature based on these 909 probes was built using PLS-3, with an RMSE in the validation set of 0.645 (within the 95% CI of RMSE determined in the training set). In IBP, other biological processes were more relevant than glycolysis in FDG uptake: RNA processing, ribosome biogenesis, protein processing, cell adhesion, cytoskeleton organization, angiogenesis and autophagy. Conclusions: This PLS-3-built signature is the first reported one that can accurately predict SUV. FDG uptake is a complex phenomenon that involves multiple biological processes, confirming the value of PET/CT in early response.

Objective and parametric methods used in functional classification disabled swimmers

Physiotherapy ◽  
2013 ◽  
Vol 21 (3) ◽  
Author(s):  
Natalia Uścinowicz ◽  
Wojciech Seidel ◽  
Paweł Zostawa ◽  
Sebastian Klich
Keyword(s):  
Medical Diagnosis ◽  
Olympic Games ◽  
Objective Evaluation ◽  
Subjective Assessment ◽  
Fair Play ◽  
Functional Classification ◽  
Kinematic Parameters ◽  
Athletes With Disabilities ◽  
Rule Out

AbstractThe recent Olympic Games in London incited much interest in the competition of disabled athletes. Various people connected with swimming, including coaches and athletes, have speculated about the fairness of competitions of disabled athletes. A constant problem are the subjective methods of classification in disabled sport. Originally, athletes with disabilities were classified according to medical diagnosis. Due to the injustice which still affects the competitors, functional classification was created shortly after. In the present review, the authors show the anomalies in the structure of the classification. The presented discovery led to the suggestion to introduce objective methods, thanks to which it would be no longer necessary to rely on the subjective assessment of the classifier. According to the authors, while using objective methods does not completely rule out the possibility of fraud by disabled athletes in the classification process, it would certainly reduce their incidence. Some of the objective methods useful for the classification of disabled athletes are: posturography, evaluation of the muscle parameters, electrogoniometric assessment, surface electromyography, and analysis of kinematic parameters. These methods have provide objective evaluation in the diagnostic sense but only if they are used in tandem. The authors demonstrate the undeniable benefits of using objective methods. Unfortunately, there are not only advantages of such solution, there also several drawbacks to be found. The conclusion of the article is the statement by the authors that it is right to use objective methods which allow to further the most important rule in sport: fair-play.

scholarly journals Molecular regulation of Snai2 in development and disease

2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser
Keyword(s):  
Transcription Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Zinc Finger Protein ◽  
Main Role ◽  
Biological Processes ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

scholarly journals Integrated transcriptomic and proteomic analysis reveals the complex molecular mechanisms underlying stone cell formation in Korla pear

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aisajan Mamat ◽  
Kuerban Tusong ◽  
Juan Xu ◽  
Peng Yan ◽  
Chuang Mei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Proteomic Analysis ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Cell Formation ◽  
Parenchyma Cell ◽  
Lignin Biosynthesis ◽  
Cell Content ◽  
Stone Cell ◽  
Fruit Samples

AbstractKorla pear (Pyrus sinkiangensis Yü) is a landrace selected from a hybrid pear species in the Xinjiang Autonomous Region in China. In recent years, pericarp roughening has been one of the major factors that adversely affects fruit quality. Compared with regular fruits, rough-skin fruits have a greater stone cell content. Stone cells compose sclerenchyma tissue that is formed by secondary thickening of parenchyma cell walls. In this work, we determined the main components of stone cells by isolating them from the pulp of rough-skin fruits at the ripening stage. Stone cell staining and apoptosis detection were then performed on fruit samples that were collected at three different developmental stages (20, 50 and 80 days after flowering (DAF)) representing the prime, late and stationary stages of stone cell differentiation, respectively. The same batches of samples were used for parallel transcriptomic and proteomic analysis to identify candidate genes and proteins that are related to SCW biogenesis in Korla pear fruits. The results showed that stone cells are mainly composed of cellulose (52%), hemicellulose (23%), lignin (20%) and a small amount of polysaccharides (3%). The periods of stone cell differentiation and cell apoptosis were synchronous and primarily occurred from 0 to 50 DAF. The stone cell components increased abundantly at 20 DAF but then decreased gradually. A total of 24,268 differentially expressed genes (DEGs) and 1011 differentially accumulated proteins (DAPs) were identified from the transcriptomic and proteomic data, respectively. We screened the DEGs and DAPs that were enriched in SCW-related pathways, including those associated with lignin biosynthesis (94 DEGs and 31 DAPs), cellulose and xylan biosynthesis (46 DEGs and 18 DAPs), S-adenosylmethionine (SAM) metabolic processes (10 DEGs and 3 DAPs), apoplastic ROS production (16 DEGs and 2 DAPs), and cell death (14 DEGs and 6 DAPs). Among the identified DEGs and DAPs, 63 significantly changed at both the transcript and protein levels during the experimental periods. In addition, the majority of these identified genes and proteins were expressed the most at the prime stage of stone cell differentiation, but their levels gradually decreased at the later stages.

scholarly journals N-Terminal Acetyltransferase Naa40p Whereabouts Put into N-Terminal Proteoform Perspective

2021 ◽  
Vol 22 (7) ◽  
pp. 3690
Author(s):  
Veronique Jonckheere ◽  
Petra Van Damme
Keyword(s):  
Amino Acid ◽  
Subcellular Localization ◽  
Nuclear Import ◽  
Ribosome Biogenesis ◽  
Regulatory Protein ◽  
Ectopic Expression ◽  
Cytoplasmic Localization ◽  
Histone H2a ◽  
Histone H4 ◽  
Nucleolar Proteins

The evolutionary conserved N-alpha acetyltransferase Naa40p is among the most selective N-terminal acetyltransferases (NATs) identified to date. Here we identified a conserved N-terminally truncated Naa40p proteoform named Naa40p25 or short Naa40p (Naa40S). Intriguingly, although upon ectopic expression in yeast, both Naa40p proteoforms were capable of restoring N-terminal acetylation of the characterized yeast histone H2A Naa40p substrate, the Naa40p histone H4 substrate remained N-terminally free in human haploid cells specifically deleted for canonical Naa40p27 or 237 amino acid long Naa40p (Naa40L), but expressing Naa40S. Interestingly, human Naa40L and Naa40S displayed differential expression and subcellular localization patterns by exhibiting a principal nuclear and cytoplasmic localization, respectively. Furthermore, Naa40L was shown to be N-terminally myristoylated and to interact with N-myristoyltransferase 1 (NMT1), implicating NMT1 in steering Naa40L nuclear import. Differential interactomics data obtained by biotin-dependent proximity labeling (BioID) further hints to context-dependent roles of Naa40p proteoforms. More specifically, with Naa40S representing the main co-translationally acting actor, the interactome of Naa40L was enriched for nucleolar proteins implicated in ribosome biogenesis and the assembly of ribonucleoprotein particles, overall indicating a proteoform-specific segregation of previously reported Naa40p activities. Finally, the yeast histone variant H2A.Z and the transcriptionally regulatory protein Lge1 were identified as novel Naa40p substrates, expanding the restricted substrate repertoire of Naa40p with two additional members and further confirming Lge1 as being the first redundant yNatA and yNatD substrate identified to date.

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