scholarly journals Systematic Screening of Penetratin’s Protein Targets by Yeast Proteome Microarrays

2022 ◽  
Vol 23 (2) ◽  
pp. 712
Author(s):  
Pramod Shah ◽  
Chien-Sheng Chen
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nucleic Acid ◽  
Biological Process ◽  
Cell Penetrating Peptides ◽  
Cellular Component ◽  
Metabolic Process ◽  
Bioactive Molecules ◽  
Protein Targets ◽  
Histatin 5 ◽  
Ribonucleoprotein Complex

Cell-penetrating peptides (CPPs) have distinct properties to translocate across cell envelope. The key property of CPPs to translocation with attached molecules has been utilized as vehicles for the delivery of several potential drug candidates that illustrate the significant effect in in-vitro experiment but fail in in-vivo experiment due to selectively permeable nature of cell envelop. Penetratin, a well-known CPP identified from the third α-helix of Antennapedia homeodomain of Drosophila, has been widely used and studied for the delivery of bioactive molecules to treat cancers, stroke, and infections caused by pathogenic organisms. Few studies have demonstrated that penetratin directly possesses antimicrobial activities against bacterial and fungal pathogens; however, the mechanism is unknown. In this study, we have utilized the power of high-throughput Saccharomyces cerevisiae proteome microarrays to screen all the potential protein targets of penetratin. Saccharomyces cerevisiae proteome microarrays assays of penetratin followed by statistical analysis depicted 123 Saccharomyces cerevisiae proteins as the protein targets of penetratin out of ~5800 Saccharomyces cerevisiae proteins. To understand the target patterns of penetratin, enrichment analyses were conducted using 123 protein targets. In biological process: ribonucleoprotein complex biogenesis, nucleic acid metabolic process, actin filament-based process, transcription, DNA-templated, and negative regulation of gene expression are a few significantly enriched terms. Cytoplasm, nucleus, and cell-organelles are enriched terms for cellular component. Protein-protein interactions network depicted ribonucleoprotein complex biogenesis, cortical cytoskeleton, and histone binding, which represent the major enriched terms for the 123 protein targets of penetratin. We also compared the protein targets of penetratin and intracellular protein targets of antifungal AMPs (Lfcin B, Histatin-5, and Sub-5). The comparison results showed few unique proteins between penetratin and AMPs. Nucleic acid metabolic process and cellular component disassembly were the common enrichment terms for penetratin and three AMPs. Penetratin shows unique enrichment items that are related to DNA biological process. Moreover, motif enrichment analysis depicted different enriched motifs in the protein targets of penetratin, LfcinB, Histatin-5, and Sub-5.

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

Role of Oxidative Phosphorylation in Histatin 5-Induced Cell Death in Saccharomyces cerevisiae

2004 ◽  
Vol 26 (23) ◽  
pp. 1781-1785 ◽  
Author(s):  
Kris De Smet ◽  
Rieka Reekmans ◽  
Roland Contreras
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Histatin 5

scholarly journals Transcriptomic inspection revealed a possible pathway regulating the formation of the high-quality brush hair in Chinese Haimen goat ( Capra hircus )

2018 ◽  
Vol 5 (1) ◽  
pp. 170907 ◽  
Author(s):  
Dejun Ji ◽  
Bo Yang ◽  
Yongjun Li ◽  
Miaoying Cai ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Biological Process ◽  
Kegg Pathway ◽  
Cellular Component ◽  
Biological Information ◽  
Capra Hircus ◽  
Molecular Function ◽  
High Quality ◽  
Type Iii ◽  
Kegg Pathways ◽  
Kegg Pathway Analysis

The high-quality brush hair, or Type III brush hair, is coarse hair but with a tip and little medulla, which uniquely grows in the cervical carina of Chinese Haimen goat ( Capra hircus ). To unveil the mechanism of the formation of Type III brush hair in Haimen goats, transcriptomic RNAseq technology was used for screening of differentially expressed genes (DEGs) in the skin samples of the Type III and the non-Type III hair goats, and these DEGs were analysed by KEGG pathway analysis. The results showed that a total of 295 DEGs were obtained, mainly from three main functional types: cellular component, molecular function and biological process. These DEGs were mainly enriched in three KEGG pathways, such as protein processing in endoplasmic reticulum, MAPK, and complement and coagulation cascades. These DEGs gave hints to a possible mechanism, under which heat stress possibly initiated the formation. The study provided some useful biological information, which could give a new view about the roles of certain factors in hair growth and give hints on the mechanism of the formation of the Type III brush hair in Chinese Haimen goat.

CP Poly(A) RNA Binding Immunity via Outside-in Glycosyltransfer with MT of BTRC-Activating L12535 and PIN1 Subnetworks for Cognition in PFC|CD14

2020 ◽  
Author(s):  
Lin Wang ◽  
Qingchun Chen ◽  
Haitao Feng ◽  
Minghu Jiang ◽  
Juxiang Huang ◽  
...  
Keyword(s):  
Immune Response ◽  
Network Inference ◽  
Rna Binding ◽  
Biological Process ◽  
Cellular Component ◽  
Innate Immune ◽  
Molecular Function ◽  
Ubiquitin Protein Ligase ◽  
The Common ◽  
Cluster Of Differentiation

Abstract Background: Ras suppressor protein 1 (L12535) and peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) common molecular and knowledge subnetworks containing microtubule associated protein 1B-MAP1B_1 (upstream) related to cognition by references were identified in human left hemisphere, based on our established significant high expression beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC)-activating downstream Gene (protein) reconstruction network inference (GRNInfer) and Database for Annotation, Visualization and Integrated Discovery (DAVID).Results: Our results show the common molecules exostosin-like glycosyltransferase 2 (EXTL2) interaction with MAP1B_1 both activating TERF1_1 with HSP90AB1 from BTRC-activating downstream GRNInfer database; The common biological process and molecular function of MAP1B_1, TERF1_1 as microtubule (MT) binding; HSP90AB1 as poly(A) RNA binding; BTRC, HSP90AB1, PIN1 as innate immune response from BTRC-activating downstream DAVID database; The common cellular component of EXTL2 at integral component of membrane; MAP1B_1, HSP90AB1, TERF1_1 at cytoplasm (CP); The common tissue distributions of L12535 and PIN1 in Prefrontal Cortex (PFC), PB cluster of differentiation (CD)14+Monocytes.Conclusions: We propose and mutual positively verify CP poly(A) RNA binding immunity via outside-in glycosyltransfer with MT of BTRC-activating L12535 and PIN1 subnetworks for cognition in PFC|CD14.

scholarly journals FRET Microscopy in Yeast

Biosensors ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 122 ◽  
Author(s):  
Skruzny ◽  
Pohl ◽  
Abella
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fluorescent Proteins ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Living Cells ◽  
Bioactive Molecules ◽  
Biophysical Processes ◽  
Microscopy Method ◽  
Fret Biosensors

Förster resonance energy transfer (FRET) microscopy is a powerful fluorescence microscopy method to study the nanoscale organization of multiprotein assemblies in vivo. Moreover, many biochemical and biophysical processes can be followed by employing sophisticated FRET biosensors directly in living cells. Here, we summarize existing FRET experiments and biosensors applied in yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, two important models of fundamental biomedical research and efficient platforms for analyses of bioactive molecules. We aim to provide a practical guide on suitable FRET techniques, fluorescent proteins, and experimental setups available for successful FRET experiments in yeasts.

scholarly journals Helicase Mechanisms During Homologous Recombination inSaccharomyces cerevisiae

2019 ◽  
Vol 48 (1) ◽  
pp. 255-273 ◽  
Author(s):  
J. Brooks Crickard ◽  
Eric C. Greene
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nucleic Acid ◽  
Homologous Recombination ◽  
Nucleic Acids ◽  
Acid Metabolism ◽  
Model Organism ◽  
Nucleic Acid Metabolism ◽  
Repair Pathway ◽  
Unidirectional Movement ◽  
Nucleoprotein Complexes

Helicases are enzymes that move, manage, and manipulate nucleic acids. They can be subdivided into six super families and are required for all aspects of nucleic acid metabolism. In general, all helicases function by converting the chemical energy stored in the bond between the gamma and beta phosphates of adenosine triphosphate into mechanical work, which results in the unidirectional movement of the helicase protein along one strand of a nucleic acid. The results of this translocation activity can range from separation of strands within duplex nucleic acids to the physical remodeling or removal of nucleoprotein complexes. In this review, we focus on describing key helicases from the model organism Saccharomyces cerevisiae that contribute to the regulation of homologous recombination, which is an essential DNA repair pathway for fixing damaged chromosomes.

scholarly journals Hedgehog Signaling Pathway and Autophagy in Cancer

2018 ◽  
Vol 19 (8) ◽  
pp. 2279 ◽  
Author(s):  
Xian Zeng ◽  
Dianwen Ju
Keyword(s):  
Drug Resistance ◽  
Hedgehog Signaling ◽  
Biological Process ◽  
Cellular Component ◽  
Hedgehog Signaling Pathway ◽  
Drug Resistant ◽  
Multiple Cancers ◽  
Success Stories ◽  
Cancer Types ◽  
Hh Signaling

Hedgehog (Hh) pathway controls complex developmental processes in vertebrates. Abnormal activation of Hh pathway is responsible for tumorigenesis and maintenance of multiple cancers, and thus addressing this represents promising therapeutic opportunities. In recent years, two Hh inhibitors have been approved for basal cell carcinoma (BCC) treatment and show extraordinary clinical outcomes. Meanwhile, a series of novel agents are being developed for the treatment of several cancers, including lung cancer, leukemia, and pancreatic cancer. Unfortunately, Hh inhibition fails to show satisfactory benefits in these cancer types compared with the success stories in BCC, highlighting the need for better understanding of Hh signaling in cancer. Autophagy, a conserved biological process for cellular component elimination, plays critical roles in the initiation, progression, and drug resistance of cancer, and therefore, implied potential to be targeted. Recent evidence demonstrated that Hh signaling interplays with autophagy in multiple cancers. Importantly, modulating this crosstalk exhibited noteworthy capability to sensitize primary and drug-resistant cancer cells to Hh inhibitors, representing an emerging opportunity to reboot the efficacy of Hh inhibition in those insensitive tumors, and to tackle drug resistance challenges. This review will highlight recent advances of Hh pathway and autophagy in cancers, and focus on their crosstalk and the implied therapeutic opportunities.

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