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Kotb Abdelmohsen

Bio: Kotb Abdelmohsen is an academic researcher from National Institutes of Health. The author has contributed to research in topics: RNA-binding protein & Gene silencing. The author has an hindex of 63, co-authored 145 publications receiving 17825 citations. Previous affiliations of Kotb Abdelmohsen include Catalan Institution for Research and Advanced Studies & University of Maryland, Baltimore.


Papers
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Book ChapterDOI
TL;DR: The chapter shows that the exposure of cells to menadione leads to the activation of a signaling pathway that results in theactivation of ERK 1/2, entailing the phosphorylation of Cx43 and a decrease in gap junctional intercellular communication in rat liver epithelial cells.
Abstract: Publisher Summary The chapter explains the methods used to delineate the preceding pathway leading from protein tyrosine phosphatase (PTPase) inhibition to connexin43 (Cx43) phosphorylation to deal with (1) receptor tyrosine kinase phosphorylation and PTPase inhibition, (2) extracellular signal-regulated kinases (ERK) activation and the use of pharmacological inhibitors, and (3) Cx43 phosphorylation and gap junctional communication (GJC). These methods are helpful in analyzing menadione-induced signaling pathways in rat liver epithelial cells. The chapter shows that the exposure of cells to menadione leads to the activation of a signaling pathway that results in the activation of ERK 1/2, entailing the phosphorylation of Cx43 and a decrease in gap junctional intercellular communication in rat liver epithelial cells. These effects are brought about by the activation of the EGFR, probably because of the inactivation of a not–yet-identified PTPase regulating the receptor. Menadione is a naphthoquinone derivative (2-methyl-1, 4-naphthoquinone) that is used clinically because of its vitamin K–like properties (it is also termed vitamin K3). It is enzymatically converted to menaquinone-4(2-methyl-3-geranyl-geranyl-1, 4-naphthoquinone, a form of vitamin K2) by mammals. Menadione is capable of inducing phosphorylation of ERK 1/2 and Cx43, resulting in attenuated GJC, which is reversed in the presence of inhibitors of MAPK/ERK kinase (MEK) 1 and MEK 2 (the kinases directly upstream of ERK 1/2) and the epidermal growth factor receptor (EGFR) tyrosine kinase.

30 citations

Journal ArticleDOI
TL;DR: Given the rising interest in the epitranscriptomic control of gene expression in aging, the incipient understanding of the chemical mRNA modifications, specifically m6A and m5C, that influence cellular senescence are discussed.
Abstract: Cellular senescence, a developmental program central to normal aging and aging pathologies, is robustly regulated at the post-transcriptional level. This regulation involves the interaction of RNA-binding proteins and noncoding RNAs with senescence-associated messenger RNAs (mRNAs). There is increasing evidence that these associations are modulated by chemical modifications of specific mRNA nucleotides which can enhance or reduce the binding of regulatory factors. Recent technological advances in mass spectrometry, next-generation sequencing, and genome mapping have improved markedly the detection of mRNA modifications. Given the rising interest in the epitranscriptomic control of gene expression in aging, we discuss our incipient understanding of the chemical mRNA modifications, specifically m6 A and m5 C, that influence cellular senescence. This article is categorized under: RNA Export and Localization > RNA Localization RNA Processing > RNA Editing and Modification.

29 citations

Journal ArticleDOI
26 Jun 2013-PLOS ONE
TL;DR: A highly sensitiveLet-7 reporter assay system is developed based on the expression of a chimeric mRNA that contains the luciferase coding region and a 3′-untranslated region (UTR) bearing two let-7-binding sites, which highlights GSK-3β as a novel therapeutic target in ovarian tumorigenesis.
Abstract: Several members of the let-7 microRNA family are downregulated in ovarian and other cancers. They are thought to act as tumor suppressors by lowering growth-promoting and anti-apoptotic proteins. In order to measure cellular let-7 levels systematically, we have developed a highly sensitive let-7 reporter assay system based on the expression of a chimeric mRNA that contains the luciferase coding region and a 3′-untranslated region (UTR) bearing two let-7-binding sites. In cells expressing the reporter construct, termed pmirGLO-let7, luciferase activity was high when let-7 was absent, while luciferase activity was low when let-7 levels were elevated. The ovarian cancer cell lines BG-1 and UCI-101 were transfected with the let-7 reporter and surveyed with a library of kinase inhibitors in order to identify pathways affecting let-7 activity. Among the inhibitors causing changes in endogenous let-7 abundance, the lowering of glycogen synthase kinase 3 (GSK-3)β function specifically increased let-7 levels and lowered luciferase activity. Similarly, silencing GSK-3β increased both mature and primary-let-7 levels in BG-1 cells, and decreased BG-1 cell survival. Further studies identified p53 as a downstream effector of the GSK-3β-mediated repression of let-7 biosynthesis. Our studies highlight GSK-3β as a novel therapeutic target in ovarian tumorigenesis.

29 citations

Journal ArticleDOI
TL;DR: A complex differential posttranscriptional regulation of cytokines by HuR in which gene dosage plays an important role is revealed, which may have significant implications in allergies and asthma, as well as autoimmune diseases and infection.
Abstract: The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear The RBP HuR binds to labile mRNAs, usually leading to increases in mRNA stability and/or translation Previous work demonstrated that HuR binds to the mRNAs encoding the Th2 transcription factor trans-acting T-cell-specific transcription factor (GATA-3) and Th2 cytokines interleukin (IL)-4 and IL-13, thereby regulating their expression By using a novel conditional HuR knockout (KO) mouse in which HuR is deleted in activated T cells, we show that Th2-polarized cells from heterozygous HuR conditional (OX40-Cre HuRfl/+) KO mice had decreased steady-state levels of Gata3, Il4 and Il13 mRNAs with little changes at the protein level Surprisingly, Th2-polarized cells from homozygous HuR conditional (OX40-Cre HuRfl/fl) KO mice showed increased Il2, Il4 and Il13 mRNA and protein via different mechanisms Specifically, Il4 was transcriptionally upregulated in HuR KO T cells, whereas Il2 and Il13 mRNA stabilities increased Additionally, when using the standard ovalbumin model of allergic airway inflammation, HuR conditional KO mice mounted a robust inflammatory response similar to mice with wild-type HuR levels These results reveal a complex differential posttranscriptional regulation of cytokines by HuR in which gene dosage plays an important role These findings may have significant implications in allergies and asthma, as well as autoimmune diseases and infection

29 citations

Journal ArticleDOI
TL;DR: The mechanisms, advantages, and weaknesses of in situ hybridization, molecular beacons, MS2 tagging and Cas-derived systems are discussed, as well as how RNA tracking can be employed to study various aspects of molecular biology.
Abstract: RNA tracking allows researchers to visualize RNA molecules in cells and tissues, providing important spatio-temporal information regarding RNA dynamics and function. Methods such as fluorescent in situ hybridization (FISH) and molecular beacons rely on complementary oligonucleotides to label and view endogenous transcripts. Other methods create artificial chimeric transcripts coupled with bacteriophage-derived coat proteins (e.g. MS2, λN) to tag molecules in live cells. In other approaches, endogenous RNAs are recognized by complementary RNAs complexed with noncatalytic Cas proteins. Each technique has its own set of strengths and limitations that must be considered when planning an experiment. Here, we discuss the mechanisms, advantages, and weaknesses of in situ hybridization, molecular beacons, MS2 tagging and Cas-derived systems, as well as how RNA tracking can be employed to study various aspects of molecular biology.

29 citations


Cited by
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Journal ArticleDOI
06 Jun 2013-Cell
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.

9,980 citations

Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Ilio Vitale3, Stuart A. Aaronson4  +183 moreInstitutions (111)
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

3,301 citations

Journal ArticleDOI
16 Jan 2014-Nature
TL;DR: Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.
Abstract: Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges — they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.

2,869 citations

Journal ArticleDOI
14 May 2007-Oncogene
TL;DR: Recent findings and hypotheses on the role of MAPK pathways in cancer are discussed, with a focus on stress-activated pathways, which largely seem to counteract malignant transformation.
Abstract: Cancer can be perceived as a disease of communication between and within cells. The aberrations are pleiotropic, but mitogen-activated protein kinase (MAPK) pathways feature prominently. Here, we discuss recent findings and hypotheses on the role of MAPK pathways in cancer. Cancerous mutations in MAPK pathways are frequently mostly affecting Ras and B-Raf in the extracellular signal-regulated kinase pathway. Stress-activated pathways, such as Jun N-terminal kinase and p38, largely seem to counteract malignant transformation. The balance and integration between these signals may widely vary in different tumours, but are important for the outcome and the sensitivity to drug therapy.

2,605 citations

Journal ArticleDOI
TL;DR: The function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development are described.
Abstract: Genomes of multicellular organisms are characterized by the pervasive expression of different types of non-coding RNAs (ncRNAs). Long ncRNAs (lncRNAs) belong to a novel heterogeneous class of ncRNAs that includes thousands of different species. lncRNAs have crucial roles in gene expression control during both developmental and differentiation processes, and the number of lncRNA species increases in genomes of developmentally complex organisms, which highlights the importance of RNA-based levels of control in the evolution of multicellular organisms. In this Review, we describe the function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development.

2,464 citations