LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: Uncovering structural themes across cilia microtubule inner proteins with implications for human cilia function.

    Andersen, Jens S / Vijayakumaran, Aaran / Godbehere, Christopher / Lorentzen, Esben / Mennella, Vito / Schou, Kenneth Bødtker

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2687

    Abstract: Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins ( ... ...

    Abstract Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address the outstanding question of how distinct MIPs evolved to recognize microtubule inner surfaces, we applied computational sequence analyses, structure predictions, and experimental validation to uncover evolutionarily conserved microtubule- and MIP-binding modules named NWE, SNYG, and ELLEn, and PYG and GFG-repeat by their signature motifs. These modules intermix with MT-binding DM10-modules and Mn-repeats in 24 Chlamydomonas and 33 human proteins. The modules molecular characteristics provided keys to identify elusive cross-species homologs, hitherto unknown human MIP candidates, and functional properties for seven protein subfamilies, including the microtubule seam-binding NWE and ELLEn families. Our work defines structural innovations that underpin centriole and axoneme assembly and demonstrates that MIPs co-evolved with centrosomes and cilia.
    MeSH term(s) Humans ; Cilia/metabolism ; Microtubule Proteins/metabolism ; Axoneme/metabolism ; Microtubules/metabolism ; Centrioles/metabolism
    Chemical Substances Microtubule Proteins
    Language English
    Publishing date 2024-03-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46737-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Ins and outs of GPCR signaling in primary cilia.

    Schou, Kenneth Bødtker / Pedersen, Lotte Bang / Christensen, Søren Tvorup

    EMBO reports

    2015  Volume 16, Issue 9, Page(s) 1099–1113

    Abstract: Primary cilia are specialized microtubule-based signaling organelles that convey extracellular signals into a cellular response in most vertebrate cell types. The physiological significance of primary cilia is underscored by the fact that defects in ... ...

    Abstract Primary cilia are specialized microtubule-based signaling organelles that convey extracellular signals into a cellular response in most vertebrate cell types. The physiological significance of primary cilia is underscored by the fact that defects in assembly or function of these organelles lead to a range of severe diseases and developmental disorders. In most cell types of the human body, signaling by primary cilia involves different G protein-coupled receptors (GPCRs), which transmit specific signals to the cell through G proteins to regulate diverse cellular and physiological events. Here, we provide an overview of GPCR signaling in primary cilia, with main focus on the rhodopsin-like (class A) and the smoothened/frizzled (class F) GPCRs. We describe how such receptors dynamically traffic into and out of the ciliary compartment and how they interact with other classes of ciliary GPCRs, such as class B receptors, to control ciliary function and various physiological and behavioral processes. Finally, we discuss future avenues for developing GPCR-targeted drug strategies for the treatment of ciliopathies.
    MeSH term(s) Animals ; Cilia/genetics ; Cilia/metabolism ; Cilia/ultrastructure ; GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Humans ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Rhodopsin/metabolism ; Signal Transduction/genetics ; Smoothened Receptor
    Chemical Substances Receptors, G-Protein-Coupled ; SMO protein, human ; Smoothened Receptor ; Rhodopsin (9009-81-8) ; GTP-Binding Proteins (EC 3.6.1.-)
    Language English
    Publishing date 2015-08-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201540530
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 41: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: Early-stage apoptosis is associated with DNA-damage-independent ATM phosphorylation and chromatin decondensation in NIH3T3 fibroblasts.

    Schou, Kenneth Bødtker / Schneider, Linda / Christensen, Søren Tvorup / Hoffmann, Else Kay

    Cell biology international

    2008  Volume 32, Issue 1, Page(s) 107–113

    Abstract: Chromatin condensation and degradation of DNA into internucleosomal DNA fragments are key hallmarks of apoptosis. The phosphorylation of protein kinase ataxia telangiectasia mutated (ATM) and histone H2A.X was recently shown to occur concurrently with ... ...

    Abstract Chromatin condensation and degradation of DNA into internucleosomal DNA fragments are key hallmarks of apoptosis. The phosphorylation of protein kinase ataxia telangiectasia mutated (ATM) and histone H2A.X was recently shown to occur concurrently with apoptotic DNA fragmentation. We have used immunofluorescence microscopy, Western blot analysis and alkali comet assays to show that phosphorylation of ATM in NIH3T3 fibroblasts occurs prior to apoptotic DNA fragmentation, nuclease degradation and phosphorylation of histone H2A.X in cells treated with low levels of either staurosporine (STS) or tumor necrosis factor-alpha mixed with cycloheximide (TNF-alpha/CHX). In extension to previous findings, ATM phosphorylation was associated with chromatin decondensation, i.e., by loss of dense foci of constitutive heterochromatin. These results suggest that chromatin is decondensed and that ATM is activated independently of DNA damage signaling pathways during the very early stages of apoptosis.
    MeSH term(s) Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Ataxia Telangiectasia Mutated Proteins ; Caspase 3/metabolism ; Cell Cycle Proteins/metabolism ; Chromatin/metabolism ; Chromatin/pathology ; Cycloheximide/pharmacology ; DNA Damage/physiology ; DNA Fragmentation/drug effects ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Hypotonic Solutions/pharmacology ; Mice ; NIH 3T3 Cells ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism ; Staurosporine/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Cell Cycle Proteins ; Chromatin ; DNA-Binding Proteins ; Hypotonic Solutions ; Tumor Necrosis Factor-alpha ; Tumor Suppressor Proteins ; Cycloheximide (98600C0908) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Atm protein, mouse (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Caspase 3 (EC 3.4.22.-) ; Staurosporine (H88EPA0A3N)
    Language English
    Publishing date 2008-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1143453-3
    ISSN 1095-8355 ; 1065-6995
    ISSN (online) 1095-8355
    ISSN 1065-6995
    DOI 10.1016/j.cellbi.2007.08.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1451: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases.

    Schmid, Fabian Marc / Schou, Kenneth Bødtker / Vilhelm, Martin Juel / Holm, Maria Schrøder / Breslin, Loretta / Farinelli, Pietro / Larsen, Lars Allan / Andersen, Jens Skorstengaard / Pedersen, Lotte Bang / Christensen, Søren Tvorup

    The Journal of cell biology

    2017  Volume 217, Issue 1, Page(s) 151–161

    Abstract: Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and ... ...

    Abstract Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRα is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor is subsequently ubiquitinated and internalized. In contrast, in IFT20-depleted cells, PDGFRα localizes aberrantly to the plasma membrane and is overactivated after ligand stimulation because of destabilization and degradation of c-Cbl and Cbl-b.
    MeSH term(s) 3T3 Cells ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Carrier Proteins/metabolism ; Cell Line ; Cilia/metabolism ; HEK293 Cells ; Humans ; Mice ; Platelet-Derived Growth Factor/pharmacology ; Proto-Oncogene Proteins c-cbl/metabolism ; RNA Interference ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Signal Transduction/genetics ; Ubiquitination/physiology
    Chemical Substances Adaptor Proteins, Signal Transducing ; Carrier Proteins ; Cblb protein, mouse ; IFT20 protein, human ; Ift20 protein, mouse ; Platelet-Derived Growth Factor ; platelet-derived growth factor A ; Proto-Oncogene Proteins c-cbl (EC 2.3.2.27) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1) ; CBL protein, human (EC 6.3.2.-)
    Language English
    Publishing date 2017-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.201611050
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.190: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR

    Danielsen, Jannie M. Rendtlew / Larsen, Dorthe Helena / Schou, Kenneth Bødtker / Freire, Raimundo / Falck, Jacob / Bartek, Jiri / Lukas, Jiri

    Journal of biological chemistry. 2009 Feb. 13, v. 284, no. 7

    2009  

    Abstract: ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling ... ...

    Abstract ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling pathway and contributes to full-scale activation of ATR kinase activity. We show that HCLK2 forms a complex with ATR-ATRIP and the ATR activator TopBP1. We demonstrate that HCLK2-induced ATR kinase activity toward substrates requires TopBP1 and vice versa and provides evidence that HCLK2 facilitates efficient ATR-TopBP1 association. Consistent with its role in ATR activation, HCLK2 depletion severely impaired phosphorylation of multiple ATR targets including Chk1, Nbs1, and Smc1 after DNA damage. We show that HCLK2 is required for and stimulates ATR autophosphorylation and activity toward different substrates in vitro. Furthermore, HCLK2 depletion abrogated the G₂ checkpoint and decreased survival of cells after exposure to DNA damaging agents and replicative stress. Overall, our data suggest that HCLK2 facilitates ATR activation and, therefore, contributes to ATR-mediated checkpoint signaling. Importantly, our results suggest that HCLK2 functions in the same pathway as TopBP1 but that the two proteins regulate different steps in ATR activation.
    Language English
    Dates of publication 2009-0213
    Size p. 4140-4147.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 65/118: Show issues
    Z 6.2: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article: HCLK2 is required for activity of the DNA damage response kinase ATR.

    Rendtlew Danielsen, Jannie M / Larsen, Dorthe Helena / Schou, Kenneth Bødtker / Freire, Raimundo / Falck, Jacob / Bartek, Jiri / Lukas, Jiri

    The Journal of biological chemistry

    2008  Volume 284, Issue 7, Page(s) 4140–4147

    Abstract: ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling ... ...

    Abstract ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling pathway and contributes to full-scale activation of ATR kinase activity. We show that HCLK2 forms a complex with ATR-ATRIP and the ATR activator TopBP1. We demonstrate that HCLK2-induced ATR kinase activity toward substrates requires TopBP1 and vice versa and provides evidence that HCLK2 facilitates efficient ATR-TopBP1 association. Consistent with its role in ATR activation, HCLK2 depletion severely impaired phosphorylation of multiple ATR targets including Chk1, Nbs1, and Smc1 after DNA damage. We show that HCLK2 is required for and stimulates ATR autophosphorylation and activity toward different substrates in vitro. Furthermore, HCLK2 depletion abrogated the G(2) checkpoint and decreased survival of cells after exposure to DNA damaging agents and replicative stress. Overall, our data suggest that HCLK2 facilitates ATR activation and, therefore, contributes to ATR-mediated checkpoint signaling. Importantly, our results suggest that HCLK2 functions in the same pathway as TopBP1 but that the two proteins regulate different steps in ATR activation.
    MeSH term(s) Ataxia Telangiectasia Mutated Proteins ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Checkpoint Kinase 1 ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Damage/physiology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Enzyme Induction/physiology ; Enzyme Stability/physiology ; HeLa Cells ; Humans ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism
    Chemical Substances Carrier Proteins ; Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; NBN protein, human ; Nuclear Proteins ; TOPBP1 protein, human ; structural maintenance of chromosome protein 1 ; Protein Kinases (EC 2.7.-) ; Clk dual-specificity kinases (EC 2.7.1.-) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; ATR protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; CHEK1 protein, human (EC 2.7.11.1) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2008-12-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M808174200
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top