The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform

Uwe Knippschild - One of the best experts on this subject based on the ideXlab platform.

  • the role of the Casein Kinase 1 ck1 family in different signaling pathways linked to cancer development
    Onkologie, 2005
    Co-Authors: Uwe Knippschild, Sonja Wolff, Georgios Giamas, C Brockschmidt, Mathias Wittau, Peter Uwe Wurl, Thorsten Eismann, Martin Stöter
    Abstract:

    The members of the Casein Kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (a, s, ?, d, e) and their splice varia

  • interaction of Casein Kinase 1 delta ck1δ with the light chain lc2 of microtubule associated protein 1a map1a
    Biochimica et Biophysica Acta, 2005
    Co-Authors: Sonja Wolff, Martin Stöter, Mathias Wittau, Zhenyu Xiao, Nadine Sussner, Uwe Knippschild
    Abstract:

    Abstract CK1δ, a member of the Casein Kinase 1 family of serine/threonine specific Kinases, has been shown to be involved in the regulation of microtubule dynamics. We have now identified a 176 aa fragment of the light chain LC2 of MAP1A (termed LC2-P16) specifically interacting with CK1δ. Two CK1δ interacting domains of LC2 were identified, located between aa 2629 and 2753 close to aa 2683 and between aa 2712 and 2805 of LC2. The two regions necessary for the interaction of LC2 with CK1δ have been mapped between aa 76–103 and aa 351–375 of CK1δ. Furthermore, LC2 has been identified as a new substrate of CK1δ. We therefore propose a model in which CK1δ could modulate microtubule dynamics by changing the phosphorylation status of the light chain LC2 of MAP1A.

  • the Casein Kinase 1 family participation in multiple cellular processes in eukaryotes
    Cellular Signalling, 2005
    Co-Authors: Uwe Knippschild, Sonja Wolff, Andreas Gocht, Nadine Huber, Jurgen Lohler, Martin Stöter
    Abstract:

    Phosphorylation of serine, threonine and tyrosine residues by cellular protein Kinases plays an important role in the regulation of various cellular processes. The serine/threonine specific Casein Kinase 1 and 2 protein Kinase families — (CK1 and CK2) — were among the first protein Kinases that had been described. In recent years our knowledge of the regulation and function of mammalian CK1 Kinase family members has rapidly increased. Extracellular stimuli, the subcellular localization of CK1 isoforms, their interaction with various cellular structures and proteins, as well as autophosphorylation and proteolytic cleavage of their C-terminal regulatory domains influence CK1 Kinase activity. Mammalian CK1 isoforms phosphorylate many different substrates among them key regulatory proteins involved in the control of cell differentiation, proliferation, chromosome segregation and circadian rhythms. Deregulation and/or the incidence of mutations in the coding sequence of CK1 isoforms have been linked to neurodegenerative diseases and cancer. This review will summarize our current knowledge about the function and regulation of mammalian CK1 isoforms.

  • ic261 a specific inhibitor of the protein Kinases Casein Kinase 1 delta and epsilon triggers the mitotic checkpoint and induces p53 dependent postmitotic effects
    Oncogene, 2000
    Co-Authors: Lars Behrend, Martin Stöter, Wolfgang Deppert, D M Milne, Linda E. Campbell, David W. Meek, Uwe Knippschild
    Abstract:

    IC261, a specific inhibitor of the protein Kinases Casein Kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects

  • interaction of Casein Kinase 1 delta ck1delta with post golgi structures microtubules and the spindle apparatus
    European Journal of Cell Biology, 2000
    Co-Authors: Lars Behrend, Martin Stöter, Jochen Heukeshoven, Gabriel Rutter, Wolfgang Deppert, Marion Kurth, Uwe Knippschild
    Abstract:

    Summary Members of the Casein Kinase 1 family of serine/threonine Kinases are highly conserved from yeast to mammals and seem to play an important role in vesicular trafficking, DNA repair, cell cycle progression and cytokinesis. We here report that in interphase cells of various mammalian species Casein Kinase 1 delta (CK1δ) specifically interacts with the trans Golgi network and cytoplasmic, granular particles that associate with microtubules. Furthermore, at mitosis CK1δ is recruited to the spindle apparatus and the centrosomes in cells, which have been exposed to DNA-damaging agents like etoposide or γ-irradiation. In addition, determination of the affinity of CK1δ to different tubulin isoforms in immunoprecipitation-Western analysis revealed a dramatically enhanced complex formation between CK1δ and tubulins from mitotic extracts after introducing DNA damage. The high affinity of CK1δ to the spindle apparatus in DNA-damaged cells and its ability to phosphorylate several microtubule-associated proteins points to a regulatory role of CK1δ at mitosis.

Jeff Kuret - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase 1 alpha associates with the tau-bearing lesions of inclusion body myositis.
    Neuroscience Letters, 2007
    Co-Authors: Theresa J. Kannanayakal, Jerry R. Mendell, Jeff Kuret
    Abstract:

    Inclusion body myositis and Alzheimer's disease are age-related disorders characterized in part by the appearance of intracellular lesions composed of filamentous aggregates of the microtubule-associated protein tau. Abnormal tau phosphorylation accompanies tau aggregation and may be an upstream pathological event in both diseases. Enzymes implicated in tau hyperphosphorylation in Alzheimer's disease include members of the Casein Kinase 1 family of phosphotransferases, a group of structurally related protein Kinases that frequently function in tandem with the ubiquitin modification system. To determine whether Casein Kinase 1 isoforms associate with degenerating muscle fibers of inclusion body myositis, muscle biopsy sections isolated from sporadic disease cases were subjected to double-label fluorescence immunohistochemistry using selective anti-Casein Kinase 1 and anti-phospho-tau antibodies. Results showed that the alpha isoform of Casein Kinase 1, but not the delta or epsilon isoforms, stained degenerating muscle fibers in all eight inclusion body myositis cases examined. Staining was almost exclusively localized to phospho-tau-bearing inclusions. These findings, which extend the molecular similarities between inclusion body myositis muscle and Alzheimer's disease brain, implicate Casein Kinase 1 alpha as one of the phosphotransferases potentially involved in tau hyperphosphorylation.

  • Casein Kinase-1 isoforms differentially associate with neurofibrillary and granulovacuolar degeneration lesions
    Acta Neuropathologica, 2006
    Co-Authors: Theresa J. Kannanayakal, Dale D. Vandre, Jeff Kuret
    Abstract:

    Alzheimer’s Disease (AD) is characterized by the appearance of neurofibrillary and granulovacuolar lesions in the brains of affected individuals. The former is composed of hyperphosphorylated aggregates of the microtubule-associated protein tau. The latter is poorly characterized but reacts strongly with anti-phosphoepitope antibodies indicating that it too accumulates phosphoproteins. Both lesions react strongly with antibodies directed against members of the Casein Kinase-1 family of phosphotransferases, a group of closely related protein Kinases that frequently function in tandem with the ubiquitin modification system. To determine whether individual members of the Casein Kinase-1 family differentially associate with AD lesions, hippocampal sections isolated from late stage cases of AD were subjected to double-label fluorescence immunohistochemistry using a panel of selective anti-Casein Kinase 1 antibodies and small-molecule fluorochromes thioflavin S and thiazin red. The resultant colocalization patterns revealed that the alpha CK1 isoform strongly correlated with thioflavin S and thiazin red fluorescence, indicating that it preferentially associated with neurofibrillary lesions. In contrast, the delta isoform staining pattern was dominated by colocalization with granulovacuolar degeneration bodies. These findings suggest that granulovacuolar and neurofibrillary lesions occupy separate populations of neurons, and implicate CK1 isoforms in the generation of lesion-associated phosphoepitopes. They also suggest a nexus between the phosphorylation and ubiquitination modifications found in both lesions.

  • Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human Casein Kinase-1.
    Biochemistry, 2006
    Co-Authors: Kelly A. Laguna, Guibin Li, Jeff Kuret
    Abstract:

    Casein Kinase-1 is a family of ubiquitous eukaryotic protein Kinases that frequently function in tandem with the ubiquitin modification system to modulate protein turnover and trafficking. In Alzheimer's disease, these enzymes colocalize with ubiquitinated lesions, including neurofibrillary tangles and granulovacuolar degeneration bodies, suggesting they also play a role in disease pathogenesis. To identify binding partners that potentially regulate or recruit these enzymes toward disease lesions, a Sos-recruitment yeast two-hybrid screen was performed with human Ckiδ (the Casein Kinase-1 isoform most closely linked to granulovacuolar degeneration bodies) and a human brain cDNA library. All interacting clones contained a single open reading frame termed Casein Kinase-1 binding protein (CK1BP). On the basis of sequence alignments, CK1BP was a structural homologue of the acidic domain of dysbindin, a component of the dystrophin-associated protein complex and the biogenesis of lysosome-related organelles com...

  • Casein Kinase 1 delta phosphorylates tau and disrupts its binding to microtubules
    Journal of Biological Chemistry, 2004
    Co-Authors: Guibin Li, Jeff Kuret
    Abstract:

    Abstract Tau hyperphosphorylation precedes neuritic lesion formation in Alzheimer's disease, suggesting it participates in the tau fibrillization reaction pathway. Candidate tau protein Kinases include members of the Casein Kinase 1 (CK1) family of phosphotransferases, which are highly overexpressed in Alzheimer's disease brain and colocalize with neuritic and granulovacuolar lesions. Here we characterized the contribution of one CK1 isoform, Ckiδ, to the phosphorylation of tau at residues Ser202/Thr205 and Ser396/Ser404 in human embryonic kidney 293 cells using immunodetection and fluorescence microscopy. Treatment of cells with membrane permeable CK1 inhibitor 3-[(2,3,6-trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261) lowered occupancy of Ser396/Ser404 phosphorylation sites by >70% at saturation, suggesting that endogenous CK1 was the major source of basal phosphorylation activity at these sites. Overexpression of Ckiδ increased CK1 enzyme activity and further raised tau phosphorylation at residues Ser202/Thr205 and Ser396/Ser404 in situ. Inhibitor IC261 reversed tau hyperphosphorylation induced by Ckiδ overexpression. Co-immunoprecipitation assays showed direct association of tau and Ckiδ in situ, consistent with tau being a Ckiδ substrate. Ckiδ overexpression also produced a decrease in the fraction of bulk tau bound to detergent-insoluble microtubules. These results suggest that Ckiδ phosphorylates tau at sites that modulate tau/microtubule binding, and that the expression pattern of Ckiδ in Alzheimer's disease is consistent with it playing an important role in tau aggregation.

  • Casein Kinase 1 is tightly associated with paired-helical filaments isolated from Alzheimer's disease brain.
    Journal of Neurochemistry, 2002
    Co-Authors: Jeff Kuret, Anthony J. Demaggio, Erik Christenson, Ginger S. Johnson, Merl F. Hoekstra
    Abstract:

    : The protein Kinase activity tightly associated with paired helical filaments (PHFs) purified from the brain tissue of individuals with Alzheimer's disease has been characterized in vitro. The activity is shown to phosphorylate Casein, an exogenous substrate, with a maximal velocity of approximately 2 nmol/min/mg, suggesting it comprises a significant component of the total protein in the PHF preparation. On the basis of substrate selectivity, isoquinoline sulfonamide inhibitor selectivity, in-gel renaturation assays, and western analysis, the activity consists of closely related members of the alpha branch of the Casein Kinase 1 family of protein Kinases. Because of its tight association with PHFs and its phosphate-directed substrate selectivity, Casein Kinase 1 is positioned to participate in the pathological hyperphosphorylation of tau protein that is observed in neurodegenerative diseases such as Alzheimer's disease.

Cristinamaria Cruciat - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase 1 and wnt β catenin signaling
    Current Opinion in Cell Biology, 2014
    Co-Authors: Cristinamaria Cruciat
    Abstract:

    Casein Kinase 1 (CK1) members play a critical and evolutionary conserved role in Wnt/β-catenin signaling. They phosphorylate several pathway components and exert a dual function, acting as both Wnt activators and Wnt inhibitors. Recent discoveries suggest that CK1 members act in a coordinated manner to regulate early responses to Wnt and notably that their enzymatic activity is regulated. Here, I provide a brief update of CK1 function and regulation in Wnt/β-catenin signaling.

  • Casein Kinase 1 and Wnt/β-catenin signaling.
    Current Opinion in Cell Biology, 2014
    Co-Authors: Cristinamaria Cruciat
    Abstract:

    Casein Kinase 1 (CK1) members play a critical and evolutionary conserved role in Wnt/β-catenin signaling. They phosphorylate several pathway components and exert a dual function, acting as both Wnt activators and Wnt inhibitors. Recent discoveries suggest that CK1 members act in a coordinated manner to regulate early responses to Wnt and notably that their enzymatic activity is regulated. Here, I provide a brief update of CK1 function and regulation in Wnt/β-catenin signaling.

  • rna helicase ddx3 is a regulatory subunit of Casein Kinase 1 in wnt β catenin signaling
    Science, 2013
    Co-Authors: Cristinamaria Cruciat, Christine Dolde, Reinoud E A De Groot, Bisei Ohkawara, Carmen Reinhard, Hendrik C Korswagen, Christof Niehrs
    Abstract:

    Casein Kinase 1 (CK1) members play key roles in numerous biological processes. They are considered “rogue” Kinases, because their enzymatic activity appears unregulated. Contrary to this notion, we have identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt–β-catenin network, where it acts as a regulatory subunit of CK1e: In a Wnt-dependent manner, DDX3 binds CK1e and directly stimulates its Kinase activity, and promotes phosphorylation of the scaffold protein dishevelled. DDX3 is required for Wnt–β-catenin signaling in mammalian cells and during Xenopus and Caenorhabditis elegans development. The results also suggest that the Kinase-stimulatory function extends to other DDX and CK1 members, opening fresh perspectives for one of the longest-studied protein Kinase families.

  • RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt–β-Catenin Signaling
    Science, 2013
    Co-Authors: Cristinamaria Cruciat, Christine Dolde, Reinoud E A De Groot, Bisei Ohkawara, Carmen Reinhard, Hendrik C Korswagen, Christof Niehrs
    Abstract:

    Casein Kinase 1 (CK1) members play key roles in numerous biological processes. They are considered “rogue” Kinases, because their enzymatic activity appears unregulated. Contrary to this notion, we have identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt–β-catenin network, where it acts as a regulatory subunit of CK1e: In a Wnt-dependent manner, DDX3 binds CK1e and directly stimulates its Kinase activity, and promotes phosphorylation of the scaffold protein dishevelled. DDX3 is required for Wnt–β-catenin signaling in mammalian cells and during Xenopus and Caenorhabditis elegans development. The results also suggest that the Kinase-stimulatory function extends to other DDX and CK1 members, opening fresh perspectives for one of the longest-studied protein Kinase families.

Anthony J. Demaggio - One of the best experts on this subject based on the ideXlab platform.

  • Casein Kinase 1 is tightly associated with paired-helical filaments isolated from Alzheimer's disease brain.
    Journal of Neurochemistry, 2002
    Co-Authors: Jeff Kuret, Anthony J. Demaggio, Erik Christenson, Ginger S. Johnson, Merl F. Hoekstra
    Abstract:

    : The protein Kinase activity tightly associated with paired helical filaments (PHFs) purified from the brain tissue of individuals with Alzheimer's disease has been characterized in vitro. The activity is shown to phosphorylate Casein, an exogenous substrate, with a maximal velocity of approximately 2 nmol/min/mg, suggesting it comprises a significant component of the total protein in the PHF preparation. On the basis of substrate selectivity, isoquinoline sulfonamide inhibitor selectivity, in-gel renaturation assays, and western analysis, the activity consists of closely related members of the alpha branch of the Casein Kinase 1 family of protein Kinases. Because of its tight association with PHFs and its phosphate-directed substrate selectivity, Casein Kinase 1 is positioned to participate in the pathological hyperphosphorylation of tau protein that is observed in neurodegenerative diseases such as Alzheimer's disease.

  • Casein Kinase 1 delta is associated with pathological accumulation of tau in several neurodegenerative diseases
    Neurobiology of Aging, 2000
    Co-Authors: Claudia Schwab, Anthony J. Demaggio, Jeff Kuret, Nupur Ghoshal, Lester I Binder, Patrick L Mcgeer
    Abstract:

    Abstract The distribution of Casein Kinase 1 δ (Ckiδ) was studied by immunohistochemistry and correlated with other pathological hallmarks in Alzheimer’s disease (AD), Down syndrome (DS), progressive supranuclear palsy (PSP), parkinsonism dementia complex of Guam (PDC), Pick’s disease (PiD), pallido-ponto-nigral degeneration (PPND), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), amyotrophic lateral sclerosis (ALS), and elderly controls. Ckiδ was found to be associated generally with granulovacuolar bodies and tau-containing neurofibrillary tangles in AD, DS, PSP, PDC, PPND, and controls, and Pick bodies and ballooned neurons in PiD. It was not associated with tau-containing inclusions in astroglia and oligodendroglia in PPND, PSP, and PDC. It was also not associated with tau-negative Lewy bodies in PD and DLB, Hirano bodies in PDC, Marinesco bodies in PD, AD, and controls and “skein”-like inclusions in anterior motor neurons in ALS. The colocalization of the Kinase Ckiδ and its apparent substrate tau suggests a function for Ckiδ in the abnormal processing of tau.

  • Casein Kinase 1 delta mrna is upregulated in alzheimer disease brain
    Brain Research, 2000
    Co-Authors: Koji Yasojima, Anthony J. Demaggio, Jeff Kuret, Edith G Mcgeer, Patrick L Mcgeer
    Abstract:

    Abstract The Casein Kinase-1 (Ck1) family are serine/threonine specific protein Kinases. They are highly associated with Alzheimer disease (AD) brain-derived tau filaments and granulovacuolar bodies. Recently we have demonstrated that one family member, Ckiδ, colocalizes with tau containing neurofibrillary tangles (NFTs) and other tau deposits in a number of neurodegenerative diseases. Here we show that the association in AD is accompanied by a sharp upregulation of Ckiδ mRNA in brain but not in peripheral organs. The degree of upregulation in AD brain is correlated with the degree of regional pathology. There was a 24.4-fold increase of Ckiδ mRNA in AD hippocampus compared with control, 8.04-fold in the amygdala, 7.45 in the entorhinal cortex and 7.30-fold in the midtemporal gyrus. These are areas with a high burden of NFTs, neuropil threads and dystrophic neurites. In areas almost devoid of this tau pathology, such as the caudate nucleus, occipital cortex and cerebellum, the increases in AD compared to control brain were only 2.21-, 1.89- and 1.87-fold, respectively. Western blot analysis showed that the upregulation of Ckiδ mRNA was paralleled by an upregulation of Ckiδ protein. These data establish that the association of Ckiδ with the tau pathology of AD is reflective of an increase in gene transcription. Since Alzheimer-like phosphoepitopes of tau can be generated by Ck1, the Ckiδ isoform may play an important role in this fundamental aspect of AD pathology.

  • Crystal Structure of a Conformation-selective Casein Kinase-1 Inhibitor
    Journal of Biological Chemistry, 2000
    Co-Authors: Neda Mashhoon, Anthony J. Demaggio, Valentina Tereshko, Stephen C. Bergmeier, Martin Egli, Merl F. Hoekstra, Jeff Kuret
    Abstract:

    Abstract Members of the Casein Kinase-1 family of protein Kinases play an essential role in cell regulation and disease pathogenesis. Unlike most protein Kinases, they appear to function as constitutively active enzymes. As a result, selective pharmacological inhibitors can play an important role in dissection of Casein Kinase-1-dependent processes. To address this need, new small molecule inhibitors of Casein Kinase-1 acting through ATP-competitive and ATP-noncompetitive mechanisms were isolated on the basis of in vitro screening. Here we report the crystal structure of 3-[(2,4,6-trimethoxyphenyl) methylidenyl]-indolin-2-one (IC261), an ATP-competitive inhibitor with differential activity among Casein Kinase-1 isoforms, in complex with the catalytic domain of fission yeast Casein Kinase-1 refined to a crystallographicR-factor of 22.4% at 2.8 A resolution. The structure reveals that IC261 stabilizes Casein Kinase-1 in a conformation midway between nucleotide substrate liganded and nonliganded conformations. We propose that adoption of this conformation by Casein Kinase-1 family members stabilizes a delocalized network of side chain interactions and results in a decreased dissociation rate of inhibitor.

  • p53 is phosphorylated in vitro and in vivo by the delta and epsilon isoforms of Casein Kinase 1 and enhances the level of Casein Kinase 1 delta in response to topoisomerase-directed drugs
    Oncogene, 1997
    Co-Authors: U Knippschild, Anthony J. Demaggio, Merl F. Hoekstra, D M Milne, Linda E. Campbell, Erik Christenson, David W. Meek
    Abstract:

    p53 is phosphorylated in vitro and in vivo by the delta and epsilon isoforms of Casein Kinase 1 and enhances the level of Casein Kinase 1 delta in response to topoisomerase-directed drugs

Martin Stöter - One of the best experts on this subject based on the ideXlab platform.

  • the role of the Casein Kinase 1 ck1 family in different signaling pathways linked to cancer development
    Onkologie, 2005
    Co-Authors: Uwe Knippschild, Sonja Wolff, Georgios Giamas, C Brockschmidt, Mathias Wittau, Peter Uwe Wurl, Thorsten Eismann, Martin Stöter
    Abstract:

    The members of the Casein Kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (a, s, ?, d, e) and their splice varia

  • interaction of Casein Kinase 1 delta ck1δ with the light chain lc2 of microtubule associated protein 1a map1a
    Biochimica et Biophysica Acta, 2005
    Co-Authors: Sonja Wolff, Martin Stöter, Mathias Wittau, Zhenyu Xiao, Nadine Sussner, Uwe Knippschild
    Abstract:

    Abstract CK1δ, a member of the Casein Kinase 1 family of serine/threonine specific Kinases, has been shown to be involved in the regulation of microtubule dynamics. We have now identified a 176 aa fragment of the light chain LC2 of MAP1A (termed LC2-P16) specifically interacting with CK1δ. Two CK1δ interacting domains of LC2 were identified, located between aa 2629 and 2753 close to aa 2683 and between aa 2712 and 2805 of LC2. The two regions necessary for the interaction of LC2 with CK1δ have been mapped between aa 76–103 and aa 351–375 of CK1δ. Furthermore, LC2 has been identified as a new substrate of CK1δ. We therefore propose a model in which CK1δ could modulate microtubule dynamics by changing the phosphorylation status of the light chain LC2 of MAP1A.

  • the Casein Kinase 1 family participation in multiple cellular processes in eukaryotes
    Cellular Signalling, 2005
    Co-Authors: Uwe Knippschild, Sonja Wolff, Andreas Gocht, Nadine Huber, Jurgen Lohler, Martin Stöter
    Abstract:

    Phosphorylation of serine, threonine and tyrosine residues by cellular protein Kinases plays an important role in the regulation of various cellular processes. The serine/threonine specific Casein Kinase 1 and 2 protein Kinase families — (CK1 and CK2) — were among the first protein Kinases that had been described. In recent years our knowledge of the regulation and function of mammalian CK1 Kinase family members has rapidly increased. Extracellular stimuli, the subcellular localization of CK1 isoforms, their interaction with various cellular structures and proteins, as well as autophosphorylation and proteolytic cleavage of their C-terminal regulatory domains influence CK1 Kinase activity. Mammalian CK1 isoforms phosphorylate many different substrates among them key regulatory proteins involved in the control of cell differentiation, proliferation, chromosome segregation and circadian rhythms. Deregulation and/or the incidence of mutations in the coding sequence of CK1 isoforms have been linked to neurodegenerative diseases and cancer. This review will summarize our current knowledge about the function and regulation of mammalian CK1 isoforms.

  • ic261 a specific inhibitor of the protein Kinases Casein Kinase 1 delta and epsilon triggers the mitotic checkpoint and induces p53 dependent postmitotic effects
    Oncogene, 2000
    Co-Authors: Lars Behrend, Martin Stöter, Wolfgang Deppert, D M Milne, Linda E. Campbell, David W. Meek, Uwe Knippschild
    Abstract:

    IC261, a specific inhibitor of the protein Kinases Casein Kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects

  • interaction of Casein Kinase 1 delta ck1delta with post golgi structures microtubules and the spindle apparatus
    European Journal of Cell Biology, 2000
    Co-Authors: Lars Behrend, Martin Stöter, Jochen Heukeshoven, Gabriel Rutter, Wolfgang Deppert, Marion Kurth, Uwe Knippschild
    Abstract:

    Summary Members of the Casein Kinase 1 family of serine/threonine Kinases are highly conserved from yeast to mammals and seem to play an important role in vesicular trafficking, DNA repair, cell cycle progression and cytokinesis. We here report that in interphase cells of various mammalian species Casein Kinase 1 delta (CK1δ) specifically interacts with the trans Golgi network and cytoplasmic, granular particles that associate with microtubules. Furthermore, at mitosis CK1δ is recruited to the spindle apparatus and the centrosomes in cells, which have been exposed to DNA-damaging agents like etoposide or γ-irradiation. In addition, determination of the affinity of CK1δ to different tubulin isoforms in immunoprecipitation-Western analysis revealed a dramatically enhanced complex formation between CK1δ and tubulins from mitotic extracts after introducing DNA damage. The high affinity of CK1δ to the spindle apparatus in DNA-damaged cells and its ability to phosphorylate several microtubule-associated proteins points to a regulatory role of CK1δ at mitosis.