Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    Language: English
    In: Small GTPases, 03 September 2018, Vol.9(5), pp.375-383
    Description: IQGAP1 is a scaffold protein involved in the assembly of adherens junctions. Our work has recently revealed a novel role for IQGAP1 in the regulation of tight junctions (TJ) through differential recruitment of claudins to the nascent TJ. Here, we discuss the potential mechanisms of this regulation,...
    Keywords: Cdc42 ; Claudins ; Exocyst ; Iqgap1 ; Tight Junctions ; Anatomy & Physiology
    ISSN: 2154-1248
    E-ISSN: 2154-1256
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Genes & development, 15 January 2013, Vol.27(2), pp.163-8
    Description: The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins. Analyses of DAP assembly revealed a hierarchy. CEP83 recruits both SCLT1 and CEP89 to centrioles. Subsequent recruitment of FBF1 and CEP164 is independent of CEP89 but mediated by SCLT1. All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. Undocked centrioles fail to recruit TTBK2 or release CP110, the two earliest modifications found on centrioles prior to cilia assembly, revealing centriole-to-membrane docking as a temporal and spatial cue promoting cilia initiation.
    Keywords: Centrioles -- Metabolism ; Cilia -- Physiology ; Intracellular Membranes -- Metabolism
    ISSN: 08909369
    E-ISSN: 1549-5477
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Nature Communications, 01 May 2018, Vol.9(1), pp.1-14
    Description: Poly ADP-ribosylation (PARylation) is a highly dynamic post-translation protein modification, but most methods only detect stable PARylation events. Here the authors develop a split-GFP-based sensor for PARylation detection in live cells and use it to identify a new centrosomal PARylation target.
    Keywords: Biology
    E-ISSN: 2041-1723
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Journal of cell science, 01 March 2015, Vol.128(5), pp.853-62
    Description: IQGAP1 is a scaffolding protein previously implicated in adherens junction formation. However, its role in the establishment or maintenance of tight junctions (TJs) has not been explored. We hypothesized that IQGAP1 could regulate TJ formation by modulating the expression and/or localization of junctional proteins, and we systematically tested this hypothesis in the model Madin-Darby canine kidney (MDCK) cell line. We find that IQGAP1 silencing enhances a transient increase in transepithelial electrical resistance (TER) observed during the early stages of TJ formation (Cereijido et al., 1978). Quantitative microscopy and biochemical experiments suggest that this effect of IQGAP1 on TJ assembly is accounted for by reduced expression and TJ recruitment of claudin 2, and increased TJ recruitment of claudin 4. Furthermore, we show that IQGAP1 also regulates TJ formation through its interactor CDC42, because IQGAP1 knockdown increases the activity of the CDC42 effector JNK and dominant-negative CDC42 prevents the increase in TER caused by IQGAP1 silencing. Hence, we provide evidence that IQGAP1 modulates TJ formation by a twofold mechanism: (1) controlling the expression and recruitment of claudin 2 and recruitment of claudin 4 to the TJ, and (2) transient inhibition of the CDC42-JNK pathway.
    Keywords: Claudin ; Iqgap1 ; Paracellular Permeability ; Polarized Epithelium ; Tight Junction ; Claudin-2 -- Metabolism ; Claudin-4 -- Metabolism ; Tight Junctions -- Metabolism ; Ras Gtpase-Activating Proteins -- Metabolism
    ISSN: 00219533
    E-ISSN: 1477-9137
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Cell Reports, 05 June 2018, Vol.23(10), pp.3042-3055
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications. Jenks et al. demonstrate that enhanced ciliogenesis can facilitate resistance to a number of kinase inhibitors. Both acquired and resistant cells show increases in cilia numbers and length and increased Hedgehog signaling. Targeting ciliogenesis or ciliary signaling overcomes kinase inhibitor resistance.
    Keywords: Cilia ; Kinase Inhibitor ; Resistance ; Hedgehog Pathway ; Fgfr ; Biology
    ISSN: 2211-1247
    E-ISSN: 2211-1247
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and de novo resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications....
    Keywords: Fgfr ; Hedgehog Pathway ; Cilia ; Kinase Inhibitor ; Resistance
    ISSN: 2211-1247
    Source: DataCite
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and de novo resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications.
    Description: This research was partly funded by the Institute of Cancer Research and by grants from Sarcoma UK (to B.E.T. [14.2014] and P.H.H. [3.2014]), Kent Cancer Trust (to M.M.), Hilfe fuer Krebskranke Kinder Frankfurt e.V. and Frankfurter Stiftung fuer Krebskranke Kinder (to J.C.), CRUK-CI Core Grant (C14303/A17197), and S.H.D. Fellowship (Wellcome Trust/Royal Society [107609]) (to M.D.R.). B.E.T. was supported by an ICR fellowship.
    Keywords: Fgfr ; Hedgehog Pathway ; Cilia ; Kinase Inhibitor ; Resistance
    Source: DSpace@Cambridge
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Cellular Signalling, 2007, Vol.19(7), pp.1602-1609
    Description: The Abl-interactor (Abi) proteins are involved in the regulation of actin polymerization and have recently been shown to modulate epidermal growth factor receptor (EGFR) endocytosis. Here we describe the identification of a novel complex between Abi-1 and the Cbl ubiquitin ligase that is induced by stimulation with EGF. Notably, an Abi-1 mutant lacking the SH3 domain (ΔSH3) fails to interact with Cbl and inhibits EGFR internalization. We show that expression of the Abi-1ΔSH3 mutant inhibits Cbl accumulation at the plasma membrane after EGF treatment. We have previously shown that the oncogenic Abl tyrosine kinase inhibits EGFR internalization. Here we report that the oncogenic Abl kinase disrupts the EGF-inducible Abi-1/Cbl complex, highlighting the importance of Abl kinases and downstream effectors in the regulation of EGFR internalization. Thus, our work reveals a new role for oncogenic Abl tyrosine kinases in the regulation of the Abi-1/Cbl protein complex and uncovers a role for the Abi-1/Cbl complex in the regulation of EGFR endocytosis.
    Keywords: Abi-1 ; Cbl ; EGF Receptor ; Endocytosis ; Abl Kinase ; Biology
    ISSN: 0898-6568
    E-ISSN: 1873-3913
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Jenks, Andrew D and Vyse, Simon and Wong, Jocelyn P and Kostaras, Eleftherios and Keller, Deborah and Burgoyne, Thomas and Shoemark, Amelia and Tsalikis, Athanasios and de la Roche, Maike and Michaelis, Martin and Cinatl, Jindrich and Huang, Paul H and Tanos, Barbara E (2018) Primary Cilia Mediate Diverse Kinase Inhibitor Resistance Mechanisms in Cancer. Cell reports, 23 (10). pp. 3042-3055.
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and de novo resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications.
    Keywords: RM Therapeutics. Pharmacology
    ISSN: 2211-1247
    Source: University of Kent
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: The Journal of cell biology, 07 October 2019, Vol.218(10), pp.3489-3505
    Description: Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum starvation results in TTBK2 redistribution from the periphery toward the root of distal appendages. Our biochemical analyses uncover CEP83 as a bona fide TTBK2 substrate with four phosphorylation sites characterized. We also demonstrate that CEP164-dependent TTBK2 recruitment to distal appendages is required for subsequent CEP83 phosphorylation. Specifically, TTBK2-dependent CEP83 phosphorylation is important for early ciliogenesis steps, including ciliary vesicle docking and CP110 removal. In summary, our results reveal a molecular mechanism of kinase regulation in ciliogenesis and identify CEP83 as a key substrate of TTBK2 during cilia initiation.
    Keywords: Ataxia ; Appendages ; Organelles ; Cilia ; Substrates ; Kinases ; Phosphorylation ; Substrates ; Phosphorylation ; Homeostasis ; Tubulin ; Homeostasis ; Phosphorylation ; Organelles ; Appendages ; Microscopy ; Kinases ; Starvation;
    ISSN: 00219525
    E-ISSN: 1540-8140
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages