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https://www.readbyqxmd.com/read/29142076/spatial-cues-and-not-spindle-pole-maturation-drive-the-asymmetry-of-astral-microtubules-between-new-and-pre-existing-spindle-poles
#1
Jette Lengefeld, Eric Yen, Xiuzhen Chen, Allen Leary, Jackie Vogel, Yves Barral
In many asymmetrically dividing cells, the microtubule-organizing centers (MTOCs; mammalian centrosome and yeast spindle pole body - SPB) nucleate more astral microtubules on one of the two spindle poles than the other. This differential activity generally correlates with the age of MTOCs and contributes to orienting the mitotic spindle within the cell. The asymmetry might results from the two MTOCs being in distinctive maturation states. We investigated this model in budding yeast. Using fluorophores with different maturation kinetics to label the outer plaque components of the SPB, we found that the Cnm67 protein is mobile, whereas Spc72 is not...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29142065/maintaining-centrosomes-and-cilia
#2
REVIEW
Sascha Werner, Ana Pimenta-Marques, Mónica Bettencourt-Dias
Centrosomes and cilia are present in organisms from all branches of the eukaryotic tree of life. These structures are composed of microtubules and various other proteins, and are required for a plethora of cell processes such as structuring the cytoskeleton, sensing the environment, and motility. Deregulation of centrosome and cilium components leads to a wide range of diseases, some of which are incompatible with life. Centrosomes and cilia are thought to be very stable and can persist over long periods of time...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29142064/the-resurrection-of-the-piddosome-emerging-roles-in-the-dna-damage-response-and-centrosome-surveillance
#3
REVIEW
Valentina Sladky, Fabian Schuler, Luca L Fava, Andreas Villunger
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29138491/sumoylation-regulates-the-localization-and-activity-of-polo-like-kinase-1-during-cell-cycle-in-the-silkworm-bombyx-mori
#4
Zhiqing Li, Qixin Cui, Jian Xu, Daojun Cheng, Xiaoyan Wang, Bingqian Li, Jae Man Lee, Qingyou Xia, Takahiro Kusakabe, Ping Zhao
Polo-like kinase 1 (Plk1) is a crucial cell cycle regulator by its specific localization and activity during cell cycle. It has been shown that the phosphorylation and ubiquitylation of Plk1 are required for its own activation and localization. Here, we report that SUMOylation regulates the activity of Plk1 in the lepidopteran insect of Bombyx mori. In the absence of SUMOylation, it causes the lost localization of Plk1 on centrosomes and kinetochores, as well as an uneven distribution in midzone. We further identify that the putative SUMOylation site of Bombyx Plk1 at lysine 466 is required for its localization on centrosomes, and K466 mutation in Plk1 could influence its interaction with Smt3/Ubc9 complex...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138111/recent-advances-in-melanoma-research-via-omics-platforms
#5
REVIEW
Carmen Rodríguez-Cerdeira, Alberto Molares-Vila, Miguel Carnero-Gregorio, Alberte Corbalán-Rivas
Melanoma has a high mortality rate and metastatic melanoma is highly resistant to conventional therapies. "Omics" fields such as proteomics and microRNA and exosome studies have provided new knowledge to complement the information generated by genomic studies. This work aimed to review the current status of biomarker discovery for melanoma through multi-"omics" platforms. A few sets of novel microRNAs and proteins are described, some of them with important implications in suppressing melanoma at different stages...
November 11, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29137675/human-hyaluronic-acid-synthase-1-promotes-malignant-transformation-via-epithelial-to-mesenchymal-transition-micronucleation-and-centrosome-abnormalities
#6
Nguyet Nguyen, Awanit Kumar, Simi Chacko, Rodney J Ouellette, Anirban Ghosh
BACKGROUND: Human hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3). Of the three, HAS1 is found to be localized more into the cytoplasmic space where it synthesizes intracellular HA. HA is a ubiquitous glycosaminoglycan, mainly present in the extracellular matrix (ECM) and on the cell surface, but are also detected intracellularly. Accumulation of HA in cancer cells, the cancer-surrounding stroma, and ECM is generally considered an independent prognostic factors for patients...
November 14, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29134478/key-factors-enhancing-sperm-fertilizing-ability-are-transferred-from-the-epididymis-to-the-spermatozoa-via-epididymosomes-in-the-domestic-cat-model
#7
Tricia Rowlison, Mary Ann Ottinger, Pierre Comizzoli
PURPOSE: Spermatozoa undergo critical changes in structure and function during the epididymal transit. Our previous studies in the domestic cat demonstrated that incidence of cenexin-a key protein involved in the centrosomal maturation-progressively increases in sperm cells from caput to cauda epididymidis. The objectives of the study were to (1) characterize mechanisms involved in transferring key factors-using the cenexin as a marker-between the epididymis and maturing sperm cells and (2) demonstrate the impact of such mechanisms on the acquisition of functional properties by spermatozoa...
November 14, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29133801/chromosome-segregation-occurs-by-microtubule-pushing-in-oocytes
#8
Kimberley Laband, Rémi Le Borgne, Frances Edwards, Marine Stefanutti, Julie C Canman, Jean-Marc Verbavatz, Julien Dumont
During cell division, spindle microtubules ensure an equal repartition of chromosomes between the two daughter cells. While the kinetochore-dependent mechanisms that drive mitotic chromosome segregation are well understood, in oocytes of most species atypical spindles assembled in absence of centrosomes entail poorly understood mechanisms of chromosome segregation. In particular, the structure(s) responsible for force generation during meiotic chromosome separation in oocytes is unclear. Using quantitative light microscopy, electron tomography, laser-mediated ablation, and genetic perturbations in the Caenorhabditis elegans oocyte, we studied the mechanism of chromosome segregation in meiosis...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133484/loss-of-e-cadherin-provides-tolerance-to-centrosome-amplification-in-epithelial-cancer-cells
#9
Alexander D Rhys, Pedro Monteiro, Christopher Smith, Malti Vaghela, Teresa Arnandis, Takuya Kato, Birgit Leitinger, Erik Sahai, Andrew McAinsh, Guillaume Charras, Susana A Godinho
Centrosome amplification is a common feature of human tumors. To survive, cancer cells cluster extra centrosomes during mitosis, avoiding the detrimental effects of multipolar divisions. However, it is unclear whether clustering requires adaptation or is inherent to all cells. Here, we show that cells have varied abilities to cluster extra centrosomes. Epithelial cells are innately inefficient at clustering even in the presence of HSET/KIFC1, which is essential but not sufficient to promote clustering. The presence of E-cadherin decreases cortical contractility during mitosis through a signaling cascade leading to multipolar divisions, and its knockout promotes clustering and survival of cells with multiple centrosomes...
November 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29128368/a-look-into-centrosome-abnormalities-in-colon-cancer-cells-how-they-arise-and-how-they-might-be-targeted-therapeutically
#10
REVIEW
Lauren E Harrison, Marina Bleiler, Charles Giardina
Cancer cells have long been noted for alterations in centrosome structure, number, and function. Colorectal cancers are interesting in this regard since two frequently mutated genes, APC and CTNNB1 (ß-catenin), encode proteins that directly interact with the centrosome and affect its ability to direct microtubule growth and establish cell polarity. Colorectal cancers also frequently display centrosome over-duplication and clustering. Efforts have been directed towards understanding how supernumerary centrosomes cluster and whether disrupting this clustering may be a way to induce aberrant/lethal mitoses of cancer cells...
November 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29127258/homozygous-mutation-in-cep19-a-gene-mutated-in-morbid-obesity-in-bardet-biedl-syndrome-with-predominant-postaxial-polydactyly
#11
Esra Yıldız Bölükbaşı, Sara Mumtaz, Muhammad Afzal, Ute Woehlbier, Sajid Malik, Aslıhan Tolun
BACKGROUND: Bardet-Biedl syndrome (BBS) is a ciliopathy with extensive phenotypic variability and genetic heterogeneity. We aimed to discover the gene mutated in a consanguineous kindred with multiple cases of a BBS phenotype. METHODS: SNP genotype data were used for linkage analysis and exome sequencing to identify mutations. Modelling and in silico analysis were performed to predict mutation severity. RESULTS: Patients had postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver...
November 10, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29126329/effect-of-benzo-a-pyrene-on-spindle-mis-orientation-and-fidelity-of-chromosome-segregation-in-lung-epithelial-beas-2b-cells
#12
Jose Thaiparambil, Oula Mansour, Randa El-Zein
Benzo[a]pyrene (B[a]P) is an environmental carcinogen found in tobacco smoke. It leads to high levels of DNA adducts in the lungs of cigarette smokers contributing to genomic instability. Alterations in the mitotic spindle apparatus play a major role in the generation of genomic instability through promoting chromosome mis-segregation and aneuploidy. To date, the effect of B[a]P exposure on altering the mitotic apparatus in normal lung epithelial cells remains unknown. In our study, BEAS-2B human bronchial epithelial cells were exposed to B[a]P and spindle dynamics were evaluated...
November 6, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29123917/the-telomere-bouquet-facilitates-meiotic-prophase-progression-and-exit-in-fission-yeast
#13
Vera Moiseeva, Hanna Amelina, Laura C Collopy, Christine A Armstrong, Siân R Pearson, Kazunori Tomita
During meiotic prophase, chromosome arrangement and oscillation promote the pairing of homologous chromosomes for meiotic recombination. This dramatic movement involves clustering of telomeres at the nuclear membrane to form the so-called telomere bouquet. In fission yeast, the telomere bouquet is formed near the spindle pole body (SPB), which is the microtubule organising centre, functionally equivalent to the metazoan centrosome. Disruption of bouquet configuration impedes homologous chromosome pairing, meiotic recombination and spindle formation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29123223/structural-basis-of-small-molecule-atpase-inhibition-of-a-human-mitotic-kinesin-motor-protein
#14
Hee-Won Park, Zhujun Ma, Haizhong Zhu, Shimin Jiang, Robert C Robinson, Sharyn A Endow
Kinesin microtubule motor proteins play essential roles in division, including attaching chromosomes to spindles and crosslinking microtubules for spindle assembly. Human kinesin-14 KIFC1 is unique in that cancer cells with amplified centrosomes are dependent on the motor for viable division because of its ability to cluster centrosomes and form bipolar spindles, but it is not required for division in almost all normal cells. Screens for small molecule inhibitors of KIFC1 have yielded several candidates for further development, but obtaining structural data to determine their sites of binding has been difficult...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121203/functional-characterization-of-tektin-1-in-motile-cilia-and-evidence-for-tekt1-as-a-new-candidate-gene-for-motile-ciliopathies
#15
Rebecca Ryan, Marion Failler, Madeline Louise Reilly, Meriem Garfa-Traore, Marion Delous, Emilie Filhol, Thérèse Reboul, Christine Bole-Feysot, Patrick Nitschké, Véronique Baudouin, Serge Amselem, Estelle Escudier, Marie Legendre, Alexandre Benmerah, Sophie Saunier
A child presenting with Mainzer-Saldino syndrome (MZSDS), characterized by renal, retinal and skeletal involvements, was also diagnosed with lung infections and airway ciliary dyskinesia. These manifestations suggested dysfunction of both primary and motile cilia, respectively. Targeted exome sequencing identified biallelic mutations in WDR19, encoding an IFT-A subunit previously associated with MZSDS-related chondrodysplasia, Jeune asphyxiating thoracic dysplasia and cranioectodermal dysplasia, linked to primary cilia dysfunction, and in TEKT1 which encodes tektin-1 an uncharacterized member of the tektin family, mutations of which may cause ciliary dyskinesia...
November 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29103955/cell-cycle-proteins-control-production-of-neutrophil-extracellular-traps
#16
Borko Amulic, Sebastian Lorenz Knackstedt, Ulrike Abu Abed, Nikolaus Deigendesch, Christopher J Harbort, Brian E Caffrey, Volker Brinkmann, Frank L Heppner, Philip W Hinds, Arturo Zychlinsky
Neutrophils are essential for immune defense and can respond to infection by releasing chromatin in the form of neutrophil extracellular traps (NETs). Here we show that NETs are induced by mitogens and accompanied by induction of cell-cycle markers, including phosphorylation of the retinoblastoma protein and lamins, nuclear envelope breakdown, and duplication of centrosomes. We identify cyclin-dependent kinases 4 and 6 (CDK4/6) as essential regulators of NETs and show that the response is inhibited by the cell-cycle inhibitor p21(Cip)...
October 31, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29103808/disc1-regulates-neurogenesis-via-modulating-kinetochore-attachment-of-ndel1-nde1-during-mitosis
#17
Fei Ye, Eunchai Kang, Chuan Yu, Xuyu Qian, Fadi Jacob, Cong Yu, Mao Mao, Randy Y C Poon, Jieun Kim, Hongjun Song, Guo-Li Ming, Mingjie Zhang
Mutations of DISC1 (disrupted-in-schizophrenia 1) have been associated with major psychiatric disorders. Despite the hundreds of DISC1-binding proteins reported, almost nothing is known about how DISC1 interacts with other proteins structurally to impact human brain development. Here we solved the high-resolution structure of DISC1 C-terminal tail in complex with its binding domain of Ndel1. Mechanistically, DISC1 regulates Ndel1's kinetochore attachment, but not its centrosome localization, during mitosis...
November 1, 2017: Neuron
https://www.readbyqxmd.com/read/29100415/the-e2f-activators-control-multiple-mitotic-regulators-and-maintain-genomic-integrity-through-sgo1-and-bubr1
#18
Miyoung Lee, Yainyrette Rivera-Rivera, Carlos S Moreno, Harold I Saavedra
The E2F1, E2F2, and E2F3a transcriptional activators control proliferation. However, how the E2F activators regulate mitosis to maintain genomic integrity is unclear. Centrosome amplification (CA) and unregulated spindle assembly checkpoint (SAC) are major generators of aneuploidy and chromosome instability (CIN) in cancer. Previously, we showed that overexpression of single E2F activators induced CA and CIN in mammary epithelial cells, and here we show that combined overexpression of E2F activators did not enhance CA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099272/centrosome-to-autophagosome-signalling-specific-gabarap-regulation-by-centriolar-satellites
#19
Justin Joachim, Sharon A Tooze
Yeast have one Atg8 protein; however, multiple Atg8 orthologs (LC3s and GABARAPs) are found in humans. We discovered that a population of the Atg8 ortholog GABARAP resides on the centrosome and the peri-centrosomal region. This centrosomal pool of GABARAP translocates to forming autophagosomes upon starvation to activate autophagosome formation in a non-hierarchical pathway. How this centrosome-to-phagophore delivery of GABARAP occurs was not understood. To address this, we have shown that the archetypal centriolar satellite protein PCM1 regulates recruitment of GABARAP to the centrosome...
November 3, 2017: Autophagy
https://www.readbyqxmd.com/read/29097729/akap350-recruits-eb1-to-the-spindle-poles-ensuring-proper-spindle-orientation-and-lumen-formation-in-3d-epithelial-cell-cultures
#20
Evangelina Almada, Facundo M Tonucci, Florencia Hidalgo, Anabela Ferretti, Solange Ibarra, Alejandro Pariani, Rodrigo Vena, Cristián Favre, Javier Girardini, Arlinet Kierbel, M Cecilia Larocca
The organization of epithelial cells to form hollow organs with a single lumen requires the accurate three-dimensional arrangement of cell divisions. Mitotic spindle orientation is defined by signaling pathways that provide molecular links between specific spots at the cell cortex and astral microtubules, which have not been fully elucidated. AKAP350 is a centrosomal/Golgi scaffold protein, implicated in the regulation of microtubule dynamics. Using 3D epithelial cell cultures, we found that cells with decreased AKAP350 expression (AKAP350KD) formed polarized cysts with abnormal lumen morphology...
November 2, 2017: Scientific Reports
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