<scp>RBM</scp>
            14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity

Shiratsuchi, Gen; Takaoka, Katsuyoshi; Ashikawa, Tomoko; Hamada, Hiroshi; Kitagawa, Daiju

doi:10.15252/embj.201488979

Cited by 34 publications

(40 citation statements)

References 57 publications

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“…Our study revealed that this variant is located within the ePPI region between STIL and RBM14 proteins, an interaction previously reported by Shiratsuchi et al. . Protein interaction and sequence variant were studied in two different publications and the association between them has not yet been described.…”

Section: Resultssupporting

confidence: 76%

Identification of Sequence Variants within Experimentally Validated Protein Interaction Sites Provides New Insights into Molecular Mechanisms of Disease Development

Škrlj

Konc

Kunej

2017

Molecular Informatics

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Protein interactions (PI) underlie complex biological processes. Protein interaction partners include DNA, RNA, ions, small chemical compounds, and proteins (protein-protein interactions; PPI). Analysis of sequence variants within regions corresponding to experimentally validated PI sites presents novel opportunities for understanding of complex diseases. Such information has not been systematically collected due to the fact that datasets are dispersed throughout databases and publications. Sequence variants and PI regions were obtained from the UniProt database. The location of the variants was compared to start and end positions of each PPI. Associations of sequence variants with phenotype were obtained from databases including COSMIC, GAD, PharmGKB, and dbSNP. We developed a catalogue of 603 sequence variants located within regions corresponding to experimentally validated PI sites, mostly PPI regions. These sequence variants were previously associated with risk for cancer, reproduction, ageing, renal, and immune system diseases. The developed catalogue connects information from different research papers and databases, represents a new layer of information and enables designing new hypotheses. It provides a baseline for prioritization of sequence variants, which may affect protein function and binding sites. The study contributes to the development of the proteogenomics field and provides new insights for understanding molecular mechanisms underlying disease development.

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Section: Resultssupporting

confidence: 76%

Identification of Sequence Variants within Experimentally Validated Protein Interaction Sites Provides New Insights into Molecular Mechanisms of Disease Development

Škrlj

Konc

Kunej

2017

Molecular Informatics

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“…Several centrosomal proteins, including Cep76, origin recognition complex 1 (ORC1), minichromosome maintenance 5 (MCM5), RNA-binding motif protein 14 (RBM14) and CDC14 are reported to suppress centriole amplification without affecting normal duplication (29, 53–57). Their mechanisms of action, however, have not been fully deciphered.…”

Section: Discussionmentioning

confidence: 99%

Opposing post-translational modifications regulate Cep76 function to suppress centriole amplification

et al. 2016

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Centrioles are critical for many cellular processes including cell division and cilia assembly. The number of centrioles within a cell is under strict control, and deregulation of centriole copy number is a hallmark of cancer. The molecular mechanisms that halt centriole amplification have not been fully elucidated. Here, we found that centrosomal protein of 76 kDa (Cep76), previously shown to restrain centriole amplification, interacts with cyclin-dependent kinase 2 (CDK2) and is a bona fide substrate of this kinase. Cep76 is preferentially phosphorylated by cyclin A/CDK2 at a single site S83, and this event is crucial to suppress centriole amplification in S phase. A novel Cep76 mutation S83C identified in a cancer patient fails to prevent centriole amplification. Mechanistically, Cep76 phosphorylation inhibits activation of polo-like kinase 1 (Plk1), thereby blocking premature centriole disengagement and subsequent amplification. Cep76 can also be acetylated, and enforced acetylation at K279 dampens the protein’s ability to inhibit amplification and precludes S83 phosphorylation. Acetylation of Cep76 normally occurs in G2 phase and correlates with loss of protein function. Our data suggest that temporal changes in posttranslational modifications of Cep76 during the cell cycle regulate its capacity to suppress centriole amplification, and its deregulation may contribute to malignancy.

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“…In an analogous manner to known spindle proteins, the spindle levels of all proteins, except GLTSCR2, increased following CHC depletion. RBM14 interacts with the centriole assembly factor STIL to prevent assembly of centriolar protein complexes, thus ensuring proper spindle assembly (51). GTSE1 is a microtubule plus-end tracking protein (ϩTIP) that binds directly to the microtubules.…”

Section: Discussionmentioning

confidence: 99%

The Clathrin-dependent Spindle Proteome

Rao

Flores‐Rodriguez

Page

et al. 2016

Molecular & Cellular Proteomics

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The mitotic spindle is required for chromosome congression and subsequent equal segregation of sister chromatids. These processes involve a complex network of signaling molecules located at the spindle. The endocytic protein, clathrin, has a "moonlighting" role during mitosis, whereby it stabilizes the mitotic spindle. The signaling pathways that clathrin participates in to achieve mitotic spindle stability are unknown. Here, we assessed the mitotic spindle proteome and phosphoproteome in clathrindepleted cells using quantitative MS/MS (data are available via ProteomeXchange with identifier PXD001603). We report a spindle proteome that consists of 3046 proteins and a spindle phosphoproteome consisting of 5157 phosphosites in 1641 phosphoproteins. Of these, 2908 (95.4%) proteins and 1636 (99.7%) phosphoproteins are known or predicted spindle-associated proteins. Clathrin-depletion from spindles resulted in dysregulation of 121 proteins and perturbed signaling to 47 phosphosites. The majority of these proteins increased in mitotic spindle abundance and six of these were validated by immunofluorescence microscopy. Functional pathway analysis confirmed the reported role of clathrin in mitotic spindle stabilization for chromosome alignment and highlighted possible new mechanisms of clathrin action. The data also revealed a novel second mitotic role for clathrin in bipolar spindle formation. Molecular & Cellular

show abstract

RBM 14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity

Cited by 34 publications

References 57 publications

Identification of Sequence Variants within Experimentally Validated Protein Interaction Sites Provides New Insights into Molecular Mechanisms of Disease Development

Identification of Sequence Variants within Experimentally Validated Protein Interaction Sites Provides New Insights into Molecular Mechanisms of Disease Development

Opposing post-translational modifications regulate Cep76 function to suppress centriole amplification

The Clathrin-dependent Spindle Proteome

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