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Erich A Nigg - One of the best experts on this subject based on the ideXlab platform.

  • novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods
    The EMBO Journal, 2011
    Co-Authors: Lis Jakobsen, K Vanselow, Marie Skogs, Yusuke Toyoda, Emma Lundberg, Ina Poser, Lasse Gaarde Falkenby, Martin V Bennetzen, Jens Westendorf, Erich A Nigg
    Abstract:

    Centrosomes in animal cells are dynamic organelles with a proteinaceous matrix of pericentriolar material assembled around a pair of centrioles. They organize the microtubule cytoskeleton and the Mitotic Spindle Apparatus. Mature centrioles are essential for biogenesis of primary cilia that mediate key signalling events. Despite recent advances, the molecular basis for the plethora of processes coordinated by centrosomes is not fully understood. We have combined protein identification and localization, using PCP-SILAC mass spectrometry, BAC transgeneOmics, and antibodies to define the constituents of human centrosomes. From a background of non-specific proteins, we distinguished 126 known and 40 candidate centrosomal proteins, of which 22 were confirmed as novel components. An antibody screen covering 4000 genes revealed an additional 113 candidates. We illustrate the power of our methods by identifying a novel set of five proteins preferentially associated with mother or daughter centrioles, comprising genes implicated in cell polarity. Pulsed labelling demonstrates a remarkable variation in the stability of centrosomal protein complexes. These spatiotemporal proteomics data provide leads to the further functional characterization of centrosomal proteins.

  • dynamic changes in nuclear architecture during mitosis on the role of protein phosphorylation in Spindle assembly and chromosome segregation
    Experimental Cell Research, 1996
    Co-Authors: Erich A Nigg, Anne Blangy, Heidi A Lane
    Abstract:

    During mitosis, the vertebrate cell nucleus undergoes profound changes in architecture. At the onset of mitosis, the nuclear envelope breaks down, the nuclear lamina is depolymerized, and interphase chromatin is condensed to chromosomes. Concomitantly, cytoplasmic microtubules are reorganized into a Mitotic Spindle Apparatus, a highly dynamic structure required for the segregation of sister chromatids. Many of the above events are controlled by reversible phosphorylation. Hence, our laboratory is interested in characterizing the kinases involved in promoting progression through mitosis and in identifying their relevant substrates. Prominent among the kinases responsible for regulating entry into mitosis is the Cdc2 kinase, the first member of the cyclin dependent kinase (Cdk) family. Recently, we found that Cdc2 phosphorylates HsEg5, a human kinesin-related motor protein associated with centrosomes and the Spindle Apparatus. Our results indicate that phosphorylation regulates the association of HsEg5 with the Mitotic Spindle and that the function of this plus-end directed motor is essential for centrosome separation and bipolar Spindle formation. Another kinase implicated in regulating progression through mitosis is Plk1 (polo-like kinase 1), the human homologue of the Drosophila gene product "polo." By antibody microinjection we have found that Plk1 is required for the functional maturation of centrosomes and hence for entry into mitosis. Furthermore, we found that microinjected anti-Plk1 antibodies caused a more severe block to cell cycle progression in diploid fibroblasts than in immortalized tumor cells. This observation hints at the existence of a checkpoint linking Cdc2 activation to the presence of functional centrosomes.

Wen Hong Shen - One of the best experts on this subject based on the ideXlab platform.

  • pten regulates eg5 to control Spindle architecture and chromosome congression during mitosis
    Nature Communications, 2016
    Co-Authors: Zhong Zhang, Meng Ouyang, Fan Yang, Hongbo Hao, Kristy L Lamb, Jingyi Yang, Yuxin Yin, Wen Hong Shen
    Abstract:

    Architectural integrity of the Mitotic Spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure Mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the Mitotic kinesin motor EG5 for proper Spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic Mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of Spindle geometry, manifested prominently by shorter Spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the Mitotic Spindle Apparatus, leading to Spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling Mitotic Spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate Mitotic phosphorylation for proper Spindle formation and faithful genomic transmission.

Shen, Wen H. - One of the best experts on this subject based on the ideXlab platform.

  • PTEN regulates EG5 to control Spindle architecture and chromosome congression during mitosis
    Nature Communications, 2016
    Co-Authors: He Jinxue, Zhang Zhong, Ouyang Meng, Yang Fan, Hao Hongbo, Lamb, Kristy L., Yang Jingyi, Yin Yuxin, Shen, Wen H.
    Abstract:

    Architectural integrity of the Mitotic Spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure Mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the Mitotic kinesin motor EG5 for proper Spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic Mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of Spindle geometry, manifested prominently by shorter Spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the Mitotic Spindle Apparatus, leading to Spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling Mitotic Spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate Mitotic phosphorylation for proper Spindle formation and faithful genomic transmission.NIH grants [R01GM100478, R01CA133008]; China Scholarship Council (CSC) ScholarshipSCI(E)ARTICLEyinyuxin@bjmu.edu.cn; wes2007@med.cornell.edu

Fan Yang - One of the best experts on this subject based on the ideXlab platform.

  • pten regulates eg5 to control Spindle architecture and chromosome congression during mitosis
    Nature Communications, 2016
    Co-Authors: Zhong Zhang, Meng Ouyang, Fan Yang, Hongbo Hao, Kristy L Lamb, Jingyi Yang, Yuxin Yin, Wen Hong Shen
    Abstract:

    Architectural integrity of the Mitotic Spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure Mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the Mitotic kinesin motor EG5 for proper Spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic Mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of Spindle geometry, manifested prominently by shorter Spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the Mitotic Spindle Apparatus, leading to Spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling Mitotic Spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate Mitotic phosphorylation for proper Spindle formation and faithful genomic transmission.

Yuxin Yin - One of the best experts on this subject based on the ideXlab platform.

  • pten regulates eg5 to control Spindle architecture and chromosome congression during mitosis
    Nature Communications, 2016
    Co-Authors: Zhong Zhang, Meng Ouyang, Fan Yang, Hongbo Hao, Kristy L Lamb, Jingyi Yang, Yuxin Yin, Wen Hong Shen
    Abstract:

    Architectural integrity of the Mitotic Spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure Mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the Mitotic kinesin motor EG5 for proper Spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic Mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of Spindle geometry, manifested prominently by shorter Spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the Mitotic Spindle Apparatus, leading to Spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling Mitotic Spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate Mitotic phosphorylation for proper Spindle formation and faithful genomic transmission.