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An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00597892" target="_blank" >RIV/68378050:_____/24:00597892 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14740/24:00137205

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/pii/S2211124724009689?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124724009689?via%3Dihub</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.celrep.2024.114618" target="_blank" >10.1016/j.celrep.2024.114618</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation

  • Original language description

    Adar null mutant mouse embryos die with aberrant double-stranded RNA (dsRNA)-driven interferon induction, and Adar Mavs double mutants, in which interferon induction is prevented, die soon after birth. Protein kinase R (Pkr) is aberrantly activated in Adar Mavs mouse pup intestines before death, intestinal crypt cells die, and intestinal villi are lost. Adar Mavs Eifak2 (Pkr) triple mutant mice rescue all defects and have longterm survival. Adenosine deaminase acting on RNA 1 (ADAR1) and PKR co-immunoprecipitate from cells, suggesting PKR inhibition by direct interaction. AlphaFold studies on an inhibitory PKR dsRNA binding domain (dsRBD)-kinase domain interaction before dsRNA binding and on an inhibitory ADAR1 dsRBD3PKR kinase domain interaction on dsRNA provide a testable model of the inhibition. Wild-type or editing- inactive human ADAR1 expressed in A549 cells inhibits activation of endogenous PKR. ADAR1 dsRNA binding is required for, but is not sufficient for, PKR inhibition. Mutating the ADAR1 dsRBD3-PKR contact prevents co-immunoprecipitation, ADAR1 inhibition of PKR activity, and co-localization of ADAR1 and PKR in cells.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

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

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2024

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Cell Reports

  • ISSN

    2211-1247

  • e-ISSN

    2211-1247

  • Volume of the periodical

    43

  • Issue of the periodical within the volume

    8

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    25

  • Pages from-to

    114618

  • UT code for WoS article

    001297074700001

  • EID of the result in the Scopus database

    2-s2.0-85201161071