• Title/Summary/Keyword: protein dynamics

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Cellular Protrusions - Lamellipodia, Filopodia, Invadopodia and Podosomes - and their Roles in Progression of Orofacial Tumours: Current Understanding

  • Alblazi, Kamila Mohamed Om;Siar, Chong Huat
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2187-2191
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    • 2015
  • Background: Protrusive structures formed by migrating and invading cells are termed lamellipodia, filopodia, invadopodia and podosomes. Lamellipodia and filopodia appear on the leading edges of migrating cells and function to command the direction of the migrating cells. Invadopodia and podosomes are special F-actin-rich matrix-degrading structures that arise on the ventral surface of the cell membrane. Invadopodia are found in a variety of carcinomatous cells including squamous cell carcinoma of head and neck region whereas podosomes are found in normal highly motile cells of mesenchymal and myelomonocytic lineage. Invadopodia-associated protein markers consisted of 129 proteins belonging to different functional classes including WASP, NWASP, cortactin, Src kinase, Arp 2/3 complex, MT1-MMP and F-actin. To date, our current understanding on the role(s) of these regulators of actin dynamics in tumors of the orofacial region indicates that upregulation of these proteins promotes invasion and metastasis in oral squamous cell carcinoma, is associated with poor/worst prognostic outcome in laryngeal cancers, contributes to the persistent growth and metastasis characteristics of salivary gland adenoid cystic carcinoma, is a significant predictor of increased cancer risk in oral mucosal premalignant lesions and enhances local invasiveness in jawbone ameloblastomas.

Depletion of PDCD4 Accelerates Stress Granule Assembly Through Sensitization of Stress Response Pathways

  • Kim, Jeeho;Chang, In Youb;Lee, Wooje;Ohn, Takbum
    • Journal of Integrative Natural Science
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    • v.12 no.4
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    • pp.127-132
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    • 2019
  • Programmed cell death 4 (PDCD4) is a novel tumor suppressor that function in the nucleus and the cytoplasm and appears to be involved in the regulation of transcription and translation. Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate when cells exposed to environmental stresses. Since PDCD4 has implicated in translation repression through direct interaction with eukaryotic translation initiation factor 4A (eIF4A), we here investigated if PDCD4 has a functional role in the process of SG assembly under oxidative stresses. Using immunofluorescence microscopy, we found that PDCD4 is localized to SGs under oxidative stresses. Next, we tested if knockdown of PDCD4 has an effect on the assembly of SG using PDCD4-specific siRNA. Interestingly, SG assembly was accelerated and this effect was caused by sensitization of phosphorylation of eIF2α and dephosphorylation of eIF4E binding protein (4E-BP). These results suggest that PDCD4 has an effect on SG dynamics and possibly involved in cap-dependent translation repression under stress conditions.

Tau mis-splicing in the pathogenesis of neurodegenerative disorders

  • Park, Sun Ah;Ahn, Sang Il;Gallo, Jean-Marc
    • BMB Reports
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    • v.49 no.8
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    • pp.405-413
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    • 2016
  • Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders.

Lessons from Yeast on Emerging Roles of the ATAD2 Protein Family in Gene Regulation and Genome Organization

  • Cattaneo, Matteo;Morozumi, Yuichi;Perazza, Daniel;Boussouar, Faycal;Jamshidikia, Mahya;Rousseaux, Sophie;Verdel, Andre;Khochbin, Saadi
    • Molecules and Cells
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    • v.37 no.12
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    • pp.851-856
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    • 2014
  • ATAD2, a remarkably conserved, yet poorly characterized factor is found upregulated and associated with poor prognosis in a variety of independent cancers in human. Studies conducted on the yeast Saccharomyces cerevisiae ATAD2 homologue, Yta7, are now indicating that the members of this family may primarily be regulators of chromatin dynamics and that their action on gene expression could only be one facet of their general activity. In this review, we present an overview of the literature on Yta7 and discuss the possibility of translating these findings into other organisms to further define the involvement of ATAD2 and other members of its family in regulating chromatin structure and function both in normal and pathological situations.

Comprehensive Analysis of Proteomic Differences between Escherichia coli K-12 and B Strains Using Multiplexed Isobaric Tandem Mass Tag (TMT) Labeling

  • Han, Mee-Jung
    • Journal of Microbiology and Biotechnology
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    • v.27 no.11
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    • pp.2028-2036
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    • 2017
  • The Escherichia coli K-12 and B strains are among the most frequently used bacterial hosts for scientific research and biotechnological applications. However, omics analyses have revealed that E. coli K-12 and B exhibit notably different genotypic and phenotypic attributes, even though they were derived from the same ancestor. In a previous study, we identified a limited number of proteins from the two strains using two-dimensional gel electrophoresis and tandem mass spectrometry (MS/MS). In this study, an in-depth analysis of the physiological behavior of the E. coli K-12 and B strains at the proteomic level was performed using six-plex isobaric tandem mass tag-based quantitative MS. Additionally, the best lysis buffer for increasing the efficiency of protein extraction was selected from three tested buffers prior to the quantitative proteomic analysis. This study identifies the largest number of proteins in the two E. coli strains reported to date and is the first to show the dynamics of these proteins. Notable differences in proteins associated with key cellular properties, including some metabolic pathways, the biosynthesis and degradation of amino acids, membrane integrity, cellular tolerance, and motility, were found between the two representative strains. Compared with previous studies, these proteomic results provide a more holistic view of the overall state of E. coli cells based on a single proteomic study and reveal significant insights into why the two strains show distinct phenotypes. Additionally, the resulting data provide in-depth information that will help fine-tune processes in the future.

Simulation of ATP Metabolism in Cardiac Excitation - Contraction Coupling

  • Matsuoka, Satoshi;Sarai, Nobuaki;Jo, Hikari;Noma, Akinori
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.19-19
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    • 2003
  • We have developed a cardiac cell model (Kyoto Model) for the sinoatrial node and ventricle, which is composed of a common set of kinetic equations of membrane ionic currents, Ca$\^$2+/dynamics of sarcoplasmic reticulum and contractile protein. To expand this model by including metabolic pathways, the intracellular ATP metabolism, which is pivotal in cardiac excitation - contraction coupling, was incorporated. ATP consumption by the sarcolemmal Na$\^$+/ pump and the Ca pump in the sarcoplasmic reticulum were calculated with stoichiometry of 3Na:2K:1ATP and 2Ca:1ATP, respectively. ATP consumption by contraction was estimated according to experimental data. Dependence of contraction on ATP and inorganic phosphate was modeled, based on data of skinned cardiac fiber. in production by mitochondrial oxidative phosphorylation was modified from Korzeniewski '||'&'||' Zoladz (2001), and creatine kinase and adenylate kinase reactions were incorporated. ATP dependence of ATP-sensitive K channel and L type Ca channel were also included.

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Regulation of the Hippo signaling pathway by ubiquitin modification

  • Kim, Youngeun;Jho, Eek-hoon
    • BMB Reports
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    • v.51 no.3
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    • pp.143-150
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    • 2018
  • The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. ${\beta}-TrCP$ is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway.

Functional Analysis of ESTs from the 14-year Root of Korean Ginseng

  • Yang, Deok-Chun;In, Jun-Gyo;Kim, Moo-Sung;Jeon, Jong-Seong
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2003.04a
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    • pp.125-125
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    • 2003
  • To assist genetic study of the root development in Panax ginseng, which is one of the most important medicinal plant, expressed sequence tags (EST) analysis was carried out. We constructed a cDNA library using the 14-year ginseng root. Partial sequences were obtained from 2,975 clone. The ESTs could be clustered into 1,991 (70.2%) non-redundant groups. Similarity search of the non-redundant ESTs against public non-redundant databases of both protein and DNA indicated that 1,553 groups show similarity to genes of blown function. These ESTs clones were divided into sixteen categories depending upon gene function. The most abundant transcripts were ribonuclease 1 (67) and ribonuclease 2 (65). Our extensive EST analysis of genes expressed in 14-year ginseng root not only contributes to the understanding of the dynamics of genome expression patterns in root organ but also adds data to the reperoire of all genomic genes.

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Localization of Autophagosome in Porcine Follicular Cumulus-oocyte Complex

  • Lee, Seunghoon;Kim, Dong-Hoon;Im, Gi-Sun;Ock, Sun-A;Ullah, Imran;Hur, Tai-Young
    • Journal of Embryo Transfer
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    • v.32 no.3
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    • pp.105-109
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    • 2017
  • Autophagy is an intracellular degradation and recycling system. Oocyte maturation is dynamic process, in which various proteins should be synthesized and degraded. In our previous study, we reported the loci of autophagosome and dynamics of autophagic activity in porcine oocytes during in vitro maturation. In this study, we verified loci of autophagosome in porcine follicular cumulus-oocyte complex by detection of microtubule-associated protein 1A/1B-light chain 3 (LC3) which is the reliable marker of autophagosome. Porcine ovary including various sizes of follicles was fixed within 1 hour after collection from slaughterhouse. After fixation, immunohistochemistry was conducted on sliced ovary tissue containing various sizes of follicles by using LC3 antibody. As a result, LC3 signal was clearly detected in both cumulus and oocytes of various sizes of follicles. We also found ring shaped signal which represent autophagosome near oocyte membrane. Most of the signals in oocytes were localized nearby cellular membrane while evenly dispersed in cumulus cells. Therefore, this result suggests that autophagy occurs in porcine COCs (cumulus-oocyte complexes) at follicular stage.

Backbone NMR Assignments of a Prokaryotic Molecular Chaperone, Hsp33 from Escherichia coli

  • Lee, Yoo-Sup;Won, Hyung-Sik
    • Journal of the Korean Magnetic Resonance Society
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    • v.16 no.2
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    • pp.172-184
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    • 2012
  • The prokaryotic molecular chaperone Hsp33 achieves its holdase activity upon response to oxidative stress particularly at elevated temperature. Despite many structural studies of Hsp33, which were conducted mainly by X-ray crystallography, the actual structures of the Hsp33 in solution remains controversial. Thus, we have initiated NMR study of the reduced, inactive Hsp33 monomer and backbone NMR assignments were obtained in the present study. Based on a series of triple resonance spectra measured on a triply isotope-[$^2H/^{13}C/^{15}N$]-labeled protein, sequence-specific assignments of the backbone amide signals observed in the 2D-[$^1H/^{15}N$]TROSY spectrum could be completed up to more than 96%. However, even considering the small portion of non-assigned resonances due to the lack of sequential connectivity, we confirmed that the total number of observed signals was quite smaller than that expected from the number of amino acid residues in Hsp33. Thus, it is postulated that peculiar dynamic properties would be involved in the solution structure of the inactive Hsp33 monomer. We expect that the present assignment data would eventually provide the most fundamental and important data for the progressing studies on the 3-dimensional structure and molecular dynamics of Hsp33, which are critical for understanding its activation process.