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  1. Article ; Online: Benchmarking network algorithms for contextualizing genes of interest.

    Abby Hill / Scott Gleim / Florian Kiefer / Frederic Sigoillot / Joseph Loureiro / Jeremy Jenkins / Melody K Morris

    PLoS Computational Biology, Vol 15, Iss 12, p e

    2019  Volume 1007403

    Abstract: Computational approaches have shown promise in contextualizing genes of interest with known molecular interactions. In this work, we evaluate seventeen previously published algorithms based on characteristics of their output and their performance in ... ...

    Abstract Computational approaches have shown promise in contextualizing genes of interest with known molecular interactions. In this work, we evaluate seventeen previously published algorithms based on characteristics of their output and their performance in three tasks: cross validation, prediction of drug targets, and behavior with random input. Our work highlights strengths and weaknesses of each algorithm and results in a recommendation of algorithms best suited for performing different tasks.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites

    Atanu Paul / Stefano Annunziato / Bo Lu / Tianliang Sun / Olivera Evrova / Lara Planas-Paz / Vanessa Orsini / Luigi M. Terracciano / Olga Charlat / Zinger Yang Loureiro / Lei Ji / Raffaella Zamponi / Frederic Sigoillot / Hong Lei / Alicia Lindeman / Carsten Russ / John S. Reece-Hoyes / Thomas B. Nicholson / Jan S. Tchorz /
    Feng Cong

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: How cell-cell contact is sensed by Hippo pathway is poorly understood. Here, the authors show that KIRREL1 functions as a feedback regulator of the mammalian Hippo pathway by sensing cell-cell interaction and recruiting SAV1 to cell-cell contacts. ...

    Abstract How cell-cell contact is sensed by Hippo pathway is poorly understood. Here, the authors show that KIRREL1 functions as a feedback regulator of the mammalian Hippo pathway by sensing cell-cell interaction and recruiting SAV1 to cell-cell contacts.
    Keywords Science ; Q
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A Genome-wide CRISPR Screen Identifies ZCCHC14 as a Host Factor Required for Hepatitis B Surface Antigen Production

    Anastasia Hyrina / Christopher Jones / Darlene Chen / Scott Clarkson / Nadire Cochran / Paul Feucht / Gregory Hoffman / Alicia Lindeman / Carsten Russ / Frederic Sigoillot / Tiffany Tsang / Kyoko Uehara / Lili Xie / Don Ganem / Meghan Holdorf

    Cell Reports, Vol 29, Iss 10, Pp 2970-2978.e

    2019  Volume 6

    Abstract: Summary: A hallmark of chronic hepatitis B (CHB) virus infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB ... ...

    Abstract Summary: A hallmark of chronic hepatitis B (CHB) virus infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A small molecule, RG7834, has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase proteins 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identify additional factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients. : Hyrina et al. employ a non-biased functional CRISPR screening approach to identify host factors regulating HBsAg expression as well as those targeted by RG7834, a HBsAg inhibitor. The screen highlighted over 60 genes and identified a mechanism by which ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing. Keywords: HBV, HBsAg, CRISPR, genome-wide screen, RG7834, ZCCHC14, TENT4B, RNA tailing
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

    Martin Schröder / Martin Renatus / Xiaoyou Liang / Fabian Meili / Thomas Zoller / Sandrine Ferrand / Francois Gauter / Xiaoyan Li / Frederic Sigoillot / Scott Gleim / Therese-Marie Stachyra / Jason R. Thomas / Damien Begue / Maryam Khoshouei / Peggy Lefeuvre / Rita Andraos-Rey / BoYee Chung / Renate Ma / Benika Pinch /
    Andreas Hofmann / Markus Schirle / Niko Schmiedeberg / Patricia Imbach / Delphine Gorses / Keith Calkins / Beatrice Bauer-Probst / Magdalena Maschlej / Matt Niederst / Rob Maher / Martin Henault / John Alford / Erik Ahrne / Luca Tordella / Greg Hollingworth / Nicolas H. Thomä / Anna Vulpetti / Thomas Radimerski / Philipp Holzer / Seth Carbonneau / Claudio R. Thoma

    Nature Communications, Vol 15, Iss 1, Pp 1-

    2024  Volume 19

    Abstract: Abstract Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug ... ...

    Abstract Abstract Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So far only a few ligases have been utilized for TPD. Interestingly, the workhorse ligase CRBN has been observed to be downregulated in settings of resistance to immunomodulatory inhibitory drugs (IMiDs). Here we show that the essential E3 ligase receptor DCAF1 can be harnessed for TPD utilizing a selective, non-covalent DCAF1 binder. We confirm that this binder can be functionalized into an efficient DCAF1-BRD9 PROTAC. Chemical and genetic rescue experiments validate specific degradation via the CRL4DCAF1 E3 ligase. Additionally, a dasatinib-based DCAF1 PROTAC successfully degrades cytosolic and membrane-bound tyrosine kinases. A potent and selective DCAF1-BTK-PROTAC (DBt-10) degrades BTK in cells with acquired resistance to CRBN-BTK-PROTACs while the DCAF1-BRD9 PROTAC (DBr-1) provides an alternative strategy to tackle intrinsic resistance to VHL-degrader, highlighting DCAF1-PROTACS as a promising strategy to overcome ligase mediated resistance in clinical settings.
    Keywords Science ; Q
    Subject code 571
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: USP7 inhibits Wnt/β-catenin signaling through promoting stabilization of Axin

    Lei Ji / Bo Lu / Raffaella Zamponi / Olga Charlat / Robert Aversa / Zinger Yang / Frederic Sigoillot / Xiaoping Zhu / Tiancen Hu / John S. Reece-Hoyes / Carsten Russ / Gregory Michaud / Jan S. Tchorz / Xiaomo Jiang / Feng Cong

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: Axin is a scaffolding protein known for its role in Wnt signalling that can be marked with a variety of post-translational modifications. Here, Cong et al. demonstrate that USP7 de-ubiquinates Axin and that canonical Wnt signaling output can be increased ...

    Abstract Axin is a scaffolding protein known for its role in Wnt signalling that can be marked with a variety of post-translational modifications. Here, Cong et al. demonstrate that USP7 de-ubiquinates Axin and that canonical Wnt signaling output can be increased with USP7 inhibitors.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Genome-wide CRISPR screening reveals genetic modifiers of mutant EGFR dependence in human NSCLC

    Hao Zeng / Johnny Castillo-Cabrera / Mika Manser / Bo Lu / Zinger Yang / Vaik Strande / Damien Begue / Raffaella Zamponi / Shumei Qiu / Frederic Sigoillot / Qiong Wang / Alicia Lindeman / John S Reece-Hoyes / Carsten Russ / Debora Bonenfant / Xiaomo Jiang / Youzhen Wang / Feng Cong

    eLife, Vol

    2019  Volume 8

    Abstract: EGFR-mutant NSCLCs frequently respond to EGFR tyrosine kinase inhibitors (TKIs). However, the responses are not durable, and the magnitude of tumor regression is variable, suggesting the existence of genetic modifiers of EGFR dependency. Here, we applied ...

    Abstract EGFR-mutant NSCLCs frequently respond to EGFR tyrosine kinase inhibitors (TKIs). However, the responses are not durable, and the magnitude of tumor regression is variable, suggesting the existence of genetic modifiers of EGFR dependency. Here, we applied a genome-wide CRISPR-Cas9 screening to identify genetic determinants of EGFR TKI sensitivity and uncovered putative candidates. We show that knockout of RIC8A, essential for G-alpha protein activation, enhanced EGFR TKI-induced cell death. Mechanistically, we demonstrate that RIC8A is a positive regulator of YAP signaling, activation of which rescued the EGFR TKI sensitizing phenotype resulting from RIC8A knockout. We also show that knockout of ARIH2, or other components in the Cullin-5 E3 complex, conferred resistance to EGFR inhibition, in part by promoting nascent protein synthesis through METAP2. Together, these data uncover a spectrum of previously unidentified regulators of EGFR TKI sensitivity in EGFR-mutant human NSCLC, providing insights into the heterogeneity of EGFR TKI treatment responses.
    Keywords CRISPR screen ; EGFR TKI resistance ; GPCR signaling ; RIC8A ; YAP signaling ; ARIH2-CUL5 complex ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  7. Article ; Online: USP7 inhibits Wnt/β-catenin signaling through promoting stabilization of Axin

    Lei Ji / Bo Lu / Raffaella Zamponi / Olga Charlat / Robert Aversa / Zinger Yang / Frederic Sigoillot / Xiaoping Zhu / Tiancen Hu / John S. Reece-Hoyes / Carsten Russ / Gregory Michaud / Jan S. Tchorz / Xiaomo Jiang / Feng Cong

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: Axin is a scaffolding protein known for its role in Wnt signalling that can be marked with a variety of post-translational modifications. Here, Cong et al. demonstrate that USP7 de-ubiquinates Axin and that canonical Wnt signaling output can be increased ...

    Abstract Axin is a scaffolding protein known for its role in Wnt signalling that can be marked with a variety of post-translational modifications. Here, Cong et al. demonstrate that USP7 de-ubiquinates Axin and that canonical Wnt signaling output can be increased with USP7 inhibitors.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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