• Login
    View Item 
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Miloslavski, Rachel
    Cohen, Elad
    Avraham, Adam
    Iluz, Yifat
    Hayouka, Zvi
    Kasir, Judith
    Mudhasani, Rajini R.
    Jones, Stephen N.
    Cybulski, Nadine
    Ruegg, Markus A.
    Larsson, Ola
    Gandin, Valentina
    Rajakumar, Arjuna
    Topisirovic, Ivan
    Meyuhas, Oded
    Show allShow less
    UMass Chan Affiliations
    Department of Cell and Developmental Biology
    Document Type
    Journal Article
    Publication Date
    2014-06-01
    Keywords
    Biochemistry
    Cell Biology
    Molecular Biology
    Molecular Genetics
    
    Metadata
    Show full item record
    Link to Full Text
    http://dx.doi.org/10.1093/jmcb/mju008
    Abstract
    Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout of TSC1 or TSC2 or overexpression of Rheb rescued TOP mRNA translation in oxygen-deprived cells. Stress-induced translational repression of these mRNAs closely correlates with the hypophosphorylated state of 4E-BP, a translational repressor. However, a series of 4E-BP loss- and gain-of-function experiments disprove a cause-and-effect relationship between the phosphorylation status of 4E-BP and the translational repression of TOP mRNAs under oxygen or growth factor deprivation. Furthermore, the repressive effect of anoxia is similar to that attained by the very efficient inhibition of mTOR activity by Torin 1, but much more pronounced than raptor or rictor knockout. Likewise, deficiency of raptor or rictor, even though it mildly downregulated basal translation efficiency of TOP mRNAs, failed to suppress the oxygen-mediated translational activation of TOP mRNAs. Finally, co-knockdown of TIA-1 and TIAR, two RNA-binding proteins previously implicated in translational repression of TOP mRNAs in amino acid-starved cells, failed to relieve TOP mRNA translation under other stress conditions. Thus, the nature of the proximal translational regulator of TOP mRNAs remains elusive. of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
    Source
    Miloslavski R, Cohen E, Avraham A, Iluz Y, Hayouka Z, Kasir J, Mudhasani R, Jones SN, Cybulski N, Rüegg MA, Larsson O, Gandin V, Rajakumar A, Topisirovic I, Meyuhas O. Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner. J Mol Cell Biol. 2014 Jun;6(3):255-66. doi: 10.1093/jmcb/mju008. Link to article on publisher's site
    DOI
    10.1093/jmcb/mju008
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/36024
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1093/jmcb/mju008
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.