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Posttranslational modification of Dishevelled

Project goals

Wnts are secreted factors and regulators of embryonic development, disease and regeneration. Mutations in the Wnt pathway are crucial in pathogenesis of many diseases, including cancer. Wnts bind Frizzled family of receptors and activate several downstream signalling pathways. The immediate downstream component necessary for transduction of all branches of Wnt signalling is a scaffolding protein Dishevelled (Dvl). In the present project, we aim to understand the biochemical nature of Wnt-dependent activation Dvl by analyzing and mapping in detail the physiologically relevant posttranslational modifications of Dvl. We plan to use several approaches of protein biochemistry, proteomics and site-directed mutagenesis to uncover and validate critical phosphorylations and other possible posttranslational modifications. We expect that our findings will increase our understanding of Wnt signal transduction and provide a basis for therapeutic interventions of Wnt-associated diseases.

Keywords

DishevelledWntposttranslational modification

Public support

  • Provider

    Academy of Sciences of the Czech Republic

  • Programme

    The research grant projects for juniors

  • Call for proposals

    Juniorské badatelské grantové projekty 6 (SAV02008-B)

  • Main participants

  • Contest type

    VS - Public tender

  • Contract ID

    KJB501630801

Alternative language

  • Project name in Czech

    Posttranslační modifikace proteinu Dishevelled

  • Annotation in Czech

    Wnty jsou sekretované proteiny, které regulují embryonální vývoj, progresi nemocí i regeneraci. Mutace v molekulární dráze aktivované proteiny Wnt jsou klíčové v patogenezi mnoha chorob, včetně rakoviny. Wnty fáží receptory z rodiny Frizzled a aktivují několik signálních drah. Všechny molekulární dráhy aktivované faktory Wnt jsou závislé na cytoplazmatickém proteinu Dishevelled (Dvl). V navrhovaném projektu chceme pochopit biochemickou podstatu aktivace Dvl ve Wnt dráze. Plánujeme analyzovat a detailnězmapovat fyziologicky relevantní posttranslační modifikace proteinu Dvl. S využitím postupů proteinové biochemie, proteomiky a místně cílené mutageneze chceme objevit a validovat klíčové fosforylace a další posttranslační modifikace proteinu Dvl. Očekáváme, že naše výsledky přispějí k poznání mechanismu signální transdukce proteinů Wnt a poskytnou informace, které jsou nezbytné pro terapeutické postupy u chorob asociovaných s poruchami Wnt dráhy.

Scientific branches

  • R&D category

    ZV - Basic research

  • CEP classification - main branch

    EB - Genetics and molecular biology

  • CEP - secondary branch

  • CEP - another secondary branch

  • 10603 - Genetics and heredity (medical genetics to be 3)
    10604 - Reproductive biology (medical aspects to be 3)
    10605 - Developmental biology
    10608 - Biochemistry and molecular biology
    10609 - Biochemical research methods
    30101 - Human genetics

Completed project evaluation

  • Provider evaluation

    V - Vynikající výsledky projektu (s mezinárodním významem atd.)

  • Project results evaluation

    In the project, post-translational modification of Dishevelled and their role in the Wnt signaling wer characterized. Our data showed that casein kinase 1 and 2 are crucial regulators of Dishevelled function.

Solution timeline

  • Realization period - beginning

    Jan 1, 2008

  • Realization period - end

    Dec 31, 2010

  • Project status

    U - Finished project

  • Latest support payment

    Mar 9, 2010

Data delivery to CEP

  • Confidentiality

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

  • Data delivery code

    CEP11-AV0-KJ-U/02:2

  • Data delivery date

    Jun 14, 2011

Finance

  • Total approved costs

    1,290 thou. CZK

  • Public financial support

    1,290 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK

Basic information

Recognised costs

1 290 CZK thou.

Public support

1 290 CZK thou.

100%


Provider

Academy of Sciences of the Czech Republic

CEP

EB - Genetics and molecular biology

Solution period

01. 01. 2008 - 31. 12. 2010