• 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 TypesKeywordsProfilesView

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Huiting, L. N.
    Samaha, Y.
    Zhang, G. L.
    Roderick, Justine E.
    Li, B.
    Anderson, N. M.
    Wang, Y. W.
    Wang, L.
    Laroche, F.
    Choi, J. W.
    Liu, C. T.
    Kelliher, Michelle A.
    Feng, H.
    Show allShow less
    UMass Chan Affiliations
    UMass Metabolic Network
    Department of Molecular, Cell and Cancer Biology
    Document Type
    Journal Article
    Publication Date
    2018-04-25
    Keywords
    Acute lymphocytic leukaemia
    Cancer microenvironment
    Amino Acids, Peptides, and Proteins
    Cancer Biology
    Cell Biology
    Cellular and Molecular Physiology
    Hemic and Lymphatic Diseases
    Neoplasms
    Therapeutics
    
    Metadata
    Show full item record
    Link to Full Text
    https://doi.org/10.1038/s41375-018-0141-x
    Abstract
    Despite the pivotal role of MYC in tumorigenesis, the mechanisms by which it promotes cancer aggressiveness remain incompletely understood. Here, we show that MYC transcriptionally upregulates the ubiquitin fusion degradation 1 (UFD1) gene in T-cell acute lymphoblastic leukemia (T-ALL). Allelic loss of ufd1 in zebrafish induces tumor cell apoptosis and impairs MYC-driven T-ALL progression but does not affect general health. As the E2 component of an endoplasmic reticulum (ER)-associated degradation (ERAD) complex, UFD1 facilitates the elimination of misfolded/unfolded proteins from the ER. We found that UFD1 inactivation in human T-ALL cells impairs ERAD, exacerbates ER stress, and induces apoptosis. Moreover, we show that UFD1 inactivation promotes the proapoptotic unfolded protein response (UPR) mediated by protein kinase RNA-like ER kinase (PERK). This effect is demonstrated by an upregulation of PERK and its downstream effector C/EBP homologous protein (CHOP), as well as a downregulation of BCL2 and BCLxL. Indeed, CHOP inactivation or BCL2 overexpression is sufficient to rescue tumor cell apoptosis induced by UFD1 knockdown. Together, our studies identify UFD1 as a critical regulator of the ER stress response and a novel contributor to MYC-mediated leukemia aggressiveness, with implications for targeted therapy in T-ALL and likely other MYC-driven cancers.
    Source

    Leukemia. 2018 Apr 25. doi: 10.1038/s41375-018-0141-x. [Epub ahead of print] Link to article on publisher's site

    DOI
    10.1038/s41375-018-0141-x
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29365
    PubMed ID
    29743725
    Related Resources

    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1038/s41375-018-0141-x
    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
    Works found in eScholarship@UMassChan are protected by copyright unless otherwise indicated.
    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.