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  • 1
    Online Resource
    Online Resource
    Phase separation underlies signaling activation of oncogenic NTRK fusions
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 42 ( 2023-10-17)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 42 ( 2023-10-17)
    Abstract: NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. However, the underlying mechanisms in oncogenesis that involve various N-terminal fusion partners of NTRK fusions remain elusive. Here, we show that NTRK fusion proteins form liquid-like condensates driven by their N-terminal fusion partners. The kinase reactions are accelerated in these condensates where the complexes for downstream signaling activation are also concentrated. Our work demonstrates that the phase separation driven by NTRK fusions is not only critical for TRK activation, but the condensates formed through phase separation serve as organizational hubs for oncogenic signaling.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2219589120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Crossing the quasi-threshold manifold of a noise-driven excitable system
    The Royal Society ; 2017
    In:  Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 473, No. 2201 ( 2017-05), p. 20170058-
    Details
    In: Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, The Royal Society, Vol. 473, No. 2201 ( 2017-05), p. 20170058-
    Abstract: We consider the noise-induced escapes in an excitable system possessing a quasi-threshold manifold, along which there exists a certain point of minimal quasi-potential. In the weak noise limit, the optimal escaping path turns out to approach this particular point asymptotically, making it analogous to an ordinary saddle. Numerical simulations are performed and an elaboration on the effect of small but finite noise is given, which shows that the ridges where the prehistory probability distribution peaks are located mainly within the region where the quasi-potential increases gently. The cases allowing anisotropic noise are discussed and we found that varying the noise term in the slow variable would dramatically raise the whole level of quasi-potentials, leading to significant changes in both patterns of optimal paths and exit locations.
    Type of Medium: Online Resource
    ISSN: 1364-5021 , 1471-2946
    URL: Article
    DOI: 10.1098/rspa.2017.0058
    Language: English
    Publisher: The Royal Society
    Publication Date: 2017
    detail.hit.zdb_id: 209241-4
    detail.hit.zdb_id: 1460987-3
    SSG: 11
    Location Call Number Limitation Availability
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