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Validation and Structural Characterization of the LEDGF/p75-MLL Interface as a New Target for the Treatment of MLL-Dependent Leukemia

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10281671" target="_blank" >RIV/00216208:11310/14:10281671 - isvavai.cz</a>

  • Alternative codes found

    RIV/61388963:_____/14:00433970

  • Result on the web

    <a href="http://cancerres.aacrjournals.org/content/74/18/5139" target="_blank" >http://cancerres.aacrjournals.org/content/74/18/5139</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1158/0008-5472.CAN-13-3602" target="_blank" >10.1158/0008-5472.CAN-13-3602</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Validation and Structural Characterization of the LEDGF/p75-MLL Interface as a New Target for the Treatment of MLL-Dependent Leukemia

  • Original language description

    Mixed lineage leukemia (MLL) fusion-driven acute leukemias represent a genetically distinct subset of leukemias with poor prognosis. MLL forms a ternary complex with the lens epithelium-derived growth factor (LEDGF/p75) and MENIN. LEDGF/p75, a chromatinreader recognizing H3K36me3 marks, contributes to the association of the MLL multiprotein complex to chromatin. Formation of this complex is critical for the development of MLL leukemia. Available X-ray data represent only a partial structure of the LEDGF/p75-MLL-MENIN complex. Using nuclear magnetic resonance spectroscopy, we identified an additional LEDGF/p75-MLL interface, which overlaps with the binding site of known LEDGF/p75 interactors-HIV-1 integrase, PogZ, and JPO2. Binding of these proteins orMLL to LEDGF/p75 is mutually exclusive. The resolved structure, as well as mutational analysis, shows that the interaction is primarily sustained via two aromatic residues of MLL (F148 and F151). Colony-forming assays in MLL-AF9(+) leuke

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    FD - Oncology and haematology

  • OECD FORD branch

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    S - Specificky vyzkum na vysokych skolach

Others

  • Publication year

    2014

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Cancer Research

  • ISSN

    0008-5472

  • e-ISSN

  • Volume of the periodical

    74

  • Issue of the periodical within the volume

    18

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    13

  • Pages from-to

    5139-5151

  • UT code for WoS article

    000342358300017

  • EID of the result in the Scopus database