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  1. Article ; Online: Novel Insights into the Biochemical Mechanism of CK1ε and its Functional Interplay with DDX3X.

    Bono, Bartolo / Franco, Giulia / Riva, Valentina / Garbelli, Anna / Maga, Giovanni

    International journal of molecular sciences

    2020  Volume 21, Issue 17

    Abstract: Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA ... ...

    Abstract Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA helicase 3 X-linked (DDX3X), involved in cancer proliferation and viral infections, has been identified as one of CK1ε substrates and its positive regulator in the Wnt/β-catenin network. However, the way by which these two proteins influence each other has not been fully clarified. In order to further investigate their interplay, we defined the kinetic parameters of CK1ε towards its substrates: ATP, casein, Dvl2 and DDX3X. CK1ε affinity for ATP depends on the nature of the substrate: increasing of casein concentrations led to an increase of Km
    MeSH term(s) Adenosine Triphosphate/metabolism ; Casein Kinase Iepsilon/genetics ; Casein Kinase Iepsilon/metabolism ; Caseins/metabolism ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/metabolism ; Humans ; Kinetics ; Phosphorylation ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances CTNNB1 protein, human ; Caseins ; Wnt Proteins ; beta Catenin ; Adenosine Triphosphate (8L70Q75FXE) ; Casein Kinase Iepsilon (EC 2.7.11.1) ; DDX3X protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
    Keywords covid19
    Language English
    Publishing date 2020-09-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21176449
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Novel Insights into the Biochemical Mechanism of CK1ε and its Functional Interplay with DDX3X

    Bono, Bartolo / Franco, Giulia / Riva, Valentina / Garbelli, Anna / Maga, Giovanni

    Abstract: Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA ... ...

    Abstract Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA helicase 3 X-linked (DDX3X), involved in cancer proliferation and viral infections, has been identified as one of CK1ε substrates and its positive regulator in the Wnt/ß-catenin network. However, the way by which these two proteins influence each other has not been fully clarified. In order to further investigate their interplay, we defined the kinetic parameters of CK1ε towards its substrates: ATP, casein, Dvl2 and DDX3X. CK1ε affinity for ATP depends on the nature of the substrate: increasing of casein concentrations led to an increase of KmATP, while increasing DDX3X reduced it. In literature, DDX3X is described to act as an allosteric activator of CK1ε. However, when we performed kinase reactions combining DDX3X and casein, we did not find a positive effect of DDX3X on casein phosphorylation by CK1ε, while both substrates were phosphorylated in a competitive manner. Moreover, CK1ε positively stimulates DDX3X ATPase activity. Our data provide a more detailed kinetic characterization on the functional interplay of these two proteins.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32899434
    Database COVID19

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  3. Article ; Online: Cells with stemness features are generated from in vitro transformed human fibroblasts.

    Bono, Bartolo / Ostano, Paola / Peritore, Martina / Gregnanin, Ilaria / Belgiovine, Cristina / Liguori, Manuela / Allavena, Paola / Chiorino, Giovanna / Chiodi, Ilaria / Mondello, Chiara

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 13838

    Abstract: Cancer stem cells (CSCs) have been involved in the maintenance, progression and relapse of several tumors, but their origin is still elusive. Here, in vitro transformed human fibroblasts (cen3tel cells) and the tumorsphere assay were used to search for ... ...

    Abstract Cancer stem cells (CSCs) have been involved in the maintenance, progression and relapse of several tumors, but their origin is still elusive. Here, in vitro transformed human fibroblasts (cen3tel cells) and the tumorsphere assay were used to search for and possibly characterize CSCs in transformed somatic cells. Cen3tel cells formed spheres showing self-renewal capacity and Sox2 overexpression, suggesting that they contained a subset of cells with CSC-like features. Sphere cells displayed deregulation of a c-MYC/miR-34a circuitry, likely associated with cell protection from apoptosis. Gene expression profiles of sphere cells revealed an extensive transcriptional reprogramming. Genes up-regulated in tumorspheres identified processes related to tumorigenesis and stemness, as cholesterol biosynthesis, apoptosis suppression, interferon and cytokine mediated signalling pathways. Sphere cells engrafted into NSG mice more rapidly than adherent cells, but both cell populations were tumorigenic. These results indicate that, during transformation, human somatic cells can acquire CSC properties, confirming the high plasticity of tumor cells. However, CSC-like cells are not the only tumorigenic population in transformed cells, indicating that the CSC phenotype and tumorigenicity can be uncoupled.
    MeSH term(s) Animals ; Carcinogenesis/pathology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/physiology ; Fibroblasts/metabolism ; Fibroblasts/physiology ; Humans ; Mice ; Mice, Inbred NOD ; Neoplasm Recurrence, Local/pathology ; Neoplastic Stem Cells/metabolism ; SOXB1 Transcription Factors/metabolism ; Signal Transduction
    Chemical Substances SOX2 protein, human ; SOXB1 Transcription Factors
    Language English
    Publishing date 2018-09-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-32197-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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