MNK1 Modulation of hnRNP A1 in Cellular Senescence
Item
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Title
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MNK1 Modulation of hnRNP A1 in Cellular Senescence
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Identifier
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d_2009_2013:eefb16e938c1:11132
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identifier
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11292
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Creator
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Ziaei, Samira,
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Contributor
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Karen Hubbard
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Date
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2011
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Language
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English
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Publisher
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City University of New York.
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Subject
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Developmental biology | Molecular biology | Genetics | Fibroblaststs | Heterogeneous nuclear ribonucleoprotein A1 | MNK1 | p38 MAPK pathway | Senescence
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Abstract
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Heterogeneous nuclear ribonucleoprotein (hnRNP) family members are the most abundant components of messenger ribonucleoprotein complexes (mRNPs) and play regulatory roles in a variety of biogenesis of mRNA. hnRNP A1 is a member of the hnRNP A/B subfamily, is highly abundant, and is involved in pre-mRNA and mRNA metabolism such as alternative splicing, mRNA export, splice site selection, mRNA turnover, and translation. Recent studies have shown that stress stimuli such as osmotic shock or UVC irradiation induce cytoplasmic accumulation of hnRNP A1. The cytoplasmic accumulation is concomitant with an increase in its phosphorylation and that requires p38 MAPK. We have previously demonstrated that hnRNP A1 protein shows diminished expression level and altered subcellular distribution in senescent HS74 fibroblasts. In this study, we observed that phosphorylated hnRNP A1 protein levels decreased as a result of MNK1 inhibition and that reciprocal binding occurs between hnRNP A1 and MNK1. These data implicate MNK1 as the kinase in the p38 MAPK pathway that activates hnRNP A1 in IMR-90 fibroblasts. Furthermore, we demonstrate that inhibition of MNK1 activity modulates the phosphorylation and subcellular distribution of hnRNP A1 protein. These results suggest a role for MNK1 in the regulation of hnRNP A1 in senescent cells. This is the first report, to our knowledge, that shows a link between MNK1 and cellular senescence.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
