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  1. Article ; Online: Harnessing the cooperation between DNA-PK and cGAS in cancer therapies: The cooperation between DNA-PK and cGAS shapes tumour immunogenicity.

    Taffoni, Clara / Schüssler, Moritz / Vila, Isabelle K / Laguette, Nadine

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2023  Volume 45, Issue 7, Page(s) e2300045

    Abstract: The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is central for the initiation of anti-tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour ...

    Abstract The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is central for the initiation of anti-tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS-STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA-dependent protein kinase (DNA-PK) complex, that recently emerged as an activator of inflammatory responses in tumour cells. We propose that stratification analyses on cGAS and DNA-PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non-canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity.
    MeSH term(s) Humans ; Carcinogenesis ; DNA ; Neoplasms/metabolism ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Protein Kinases ; Animals
    Chemical Substances DNA (9007-49-2) ; Nucleotidyltransferases (EC 2.7.7.-) ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202300045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Harnessing the cooperation between DNA‐PK and cGAS in cancer therapies: The cooperation between DNA‐PK and cGAS shapes tumour immunogenicity: The cooperation between DNA‐PK and cGAS shapes tumour immunogenicity

    Taffoni, Clara / Schüssler, Moritz / Vila, Isabelle K. / Laguette, Nadine

    BioEssays. 2023 July, v. 45, no. 7 p.e2300045-

    2023  

    Abstract: The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour ...

    Abstract The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses in tumour cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity.
    Keywords carcinogenesis ; immunogenicity ; interferons ; neoplasms ; protein kinases
    Language English
    Dates of publication 2023-07
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202300045
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Gene editing of

    Schüssler, Moritz / Schott, Kerstin / Fuchs, Nina Verena / Oo, Adrian / Zahadi, Morssal / Rauch, Paula / Kim, Baek / König, Renate

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Sterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) and a potent restriction factor for immunodeficiency virus 1 (HIV-1), active in myeloid and resting ... ...

    Abstract Sterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) and a potent restriction factor for immunodeficiency virus 1 (HIV-1), active in myeloid and resting CD4
    Language English
    Publishing date 2023-08-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.24.554731
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Gene editing of

    Schüssler, Moritz / Schott, Kerstin / Fuchs, Nina Verena / Oo, Adrian / Zahadi, Morssal / Rauch, Paula / Kim, Baek / König, Renate

    mBio

    2023  Volume 14, Issue 5, Page(s) e0225223

    Abstract: Importance: We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral ... ...

    Abstract Importance: We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral restriction and the control of cellular dNTP levels in an endogenous, physiologically relevant context. A proper understanding of the mechanism of the anti-viral function of SAMHD1 will provide attractive strategies aiming at selectively manipulating SAMHD1 without affecting other cellular functions. Even more, our toolkit may inspire further genetic analysis and investigation of restriction factors inhibiting retroviruses and their cellular function and regulation, leading to a deeper understanding of intrinsic anti-viral immunity.
    MeSH term(s) HIV-1 ; SAM Domain and HD Domain-Containing Protein 1/genetics ; SAM Domain and HD Domain-Containing Protein 1/metabolism ; Gene Editing ; Nucleotides/metabolism ; Macrophages
    Chemical Substances SAM Domain and HD Domain-Containing Protein 1 (EC 3.1.5.-) ; Nucleotides
    Language English
    Publishing date 2023-10-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.02252-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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