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https://www.readbyqxmd.com/read/28633033/centrosome-assembly-reconstructing-the-core-cartwheel-structure-in%C3%A2-vitro
#1
Gaëlle Marteil, Marco António Dias Louro, Mónica Bettencourt-Dias
Centrioles are microtubule-based cylinders essential for the formation of centrosomes and cilia. A recent study provides a new cell-free assay that reconstitutes the initial structure formed during centriole assembly - the cartwheel - and proposes a new model for its formation and growth.
June 19, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28633031/cell-division-centrosomes-have-separation-anxiety
#2
Stephen R Norris, Ryoma Ohi
Prior to mitosis, duplicated centrosomes are tethered together, which is thought to prevent mitotic defects. A new study establishes the role of tetrameric Kif25, a microtubule minus-end-directed kinesin-14 motor, in preventing premature centrosome separation through a microtubule-dependent pathway.
June 19, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28632150/centrosomal-protein-70-is-a-mediator-of-paclitaxel-sensitivity
#3
Xingjuan Shi, Yujue Wang, Xiaoou Sun, Chan Wang, Peng Jiang, Yu Zhang, Qinghai Huang, Xiangdong Liu, Dengwen Li, Jun Zhou, Min Liu
Centrosome aberrations have been implicated in the development and progression of breast cancer. Our previous worked show that centrosomal protein 70 (Cep70) regulates breast cancer growth and metastasis. However, it remains elusive whether Cep70 is implicated in the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. Here we provide evidence that Cep70 is a mediator of paclitaxel sensitivity in breast cancer. Cell proliferation assays show that Cep70 expression correlates with paclitaxel sensitivity in breast cancer cell lines...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28627616/distinct-cellular-phenotype-linked-to-defective-dna-interstrand-crosslink-repair-and-homologous-recombination
#4
Aleksandra M Gorniewska, Katarzyna Kluzek, Lidia Gackowska, Izabela Kubiszewska, Malgorzata Z Zdzienicka, Aneta Bialkowska
Repair of DNA interstrand crosslinks (ICLs) predominantly involves the Fanconi anemia (FA) pathway and homologous recombination (HR). The HR repair system eliminates DNA double strand breaks (DSBs) that emerge during ICLs removal. The current study presents a novel cell line, CL‑V8B, representing a new complementation group of Chinese hamster cell mutants hypersensitive to DNA crosslinking factors. CL‑V8B exhibits increased sensitivity to various DNA‑damaging agents, including compounds leading to DSBs formation (bleomycin and 6‑thioguanine), and is extremely sensitive to poly (ADP-ribose) polymerase inhibitor (>400‑fold), which is typical for HR‑defective cells...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626028/excess-centrosomes-induce-p53-dependent-senescence-without-dna-damage-in-endothelial-cells
#5
Zhixian Yu, Dana L Ruter, Erich J Kushner, Victoria L Bautch
Tumor blood vessels support tumor growth and progression. Centrosomes are microtubule organization centers in cells, and often up to 30% of tumor endothelial cells (ECs) acquire excess (>2) centrosomes. Although excess centrosomes can lead to aneuploidy and chromosome instability in tumor cells, how untransformed ECs respond to excess centrosomes is poorly understood. We found that the frequency of primary human ECs with excess centrosomes was quickly reduced in a p53-dependent manner. Excess centrosomes in ECs were associated with p53 phosphorylation at Ser33, increased p21 levels, and decreased cell proliferation and expression of senescence markers, but independent of DNA damage and apoptosis...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28625565/the-cep19-rabl2-gtpase-complex-binds-ift-b-to-initiate-intraflagellar-transport-at-the-ciliary-base
#6
Tomoharu Kanie, Keene Louis Abbott, Nancie Ann Mooney, Edward Douglas Plowey, Janos Demeter, Peter Kent Jackson
Highly conserved intraflagellar transport (IFT) protein complexes direct both the assembly of primary cilia and the trafficking of signaling molecules. IFT complexes initially accumulate at the base of the cilium and periodically enter the cilium, suggesting an as-yet-unidentified mechanism that triggers ciliary entry of IFT complexes. Using affinity-purification and mass spectrometry of interactors of the centrosomal and ciliopathy protein, CEP19, we identify CEP350, FOP, and the RABL2B GTPase as proteins organizing the first known mechanism directing ciliary entry of IFT complexes...
June 14, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28624967/routes-and-machinery-of-primary-cilium-biogenesis
#7
REVIEW
Miguel Bernabé-Rubio, Miguel A Alonso
Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells...
June 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28621416/all-in-one-integrating-cell-polarity-meiosis-mitosis-and-mechanical-forces-in-early-oocyte-differentiation-in-vertebrates
#8
Yaniv M Elkouby
While the differentiation of oocytes is key for embryonic development, and its investigation is crucial for advancing our understanding of human reproduction and fertility, many fundamental questions in oogenesis have been long standing. However, recent technical advances have led to several breakthroughs mainly in mice and zebrafish. Here I review these recent findings, including regulation and organization of the germline cyst, the mechanistics of chromosomal pairing, establishment of cell polarity, and formation of a universal mRNA-protein (mRNP) granule called the Balbiani body...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28620049/the-x-linked-deubiquitinase-usp9x-is-an-integral-component-of-centrosome
#9
Qian Wang, Yiman Tang, Yue Xu, Shilei Xu, Yong Jiang, Qiuping Dong, Yongsheng Zhou, Wenshu Ge
The X-linked deubiquitinase USP9X has been implicated in multiple pathological disorders including malignancies and X-linked intellectual disability. However, its biological function and substrate repertoire remain to be investigated. In this study, we utilized the TMT (tandem mass tags) labeling assay to identify USP9X regulated proteins, and revealed that the expression of multiple genes is altered in USP9X deficient cells. Interestingly, we showed that USP9X promotes stabilization of centrosome protein PCM1 and CEP55 through its catalytic activity...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28619713/molecular-model-of-fission-yeast-centrosome-assembly-determined-by-superresolution-imaging
#10
Andrew J Bestul, Zulin Yu, Jay R Unruh, Sue L Jaspersen
Microtubule-organizing centers (MTOCs), known as centrosomes in animals and spindle pole bodies (SPBs) in fungi, are important for the faithful distribution of chromosomes between daughter cells during mitosis as well as for other cellular functions. The cytoplasmic duplication cycle and regulation of the Schizosaccharomyces pombe SPB is analogous to centrosomes, making it an ideal model to study MTOC assembly. Here, we use superresolution structured illumination microscopy with single-particle averaging to localize 14 S...
June 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28615197/microtubule-regulation-and-function-during-virus-infection
#11
Mojgan H Naghavi, Derek Walsh
Microtubules (MTs) form a rapidly adaptable network of filaments that radiate throughout the cell. These dynamic arrays facilitate a wide range of cellular processes including the capture, transport and spatial organization of cargos and organelles, as well as changes in cell shape, polarity and motility. Nucleating from MT organizing centers including, but by no means limited to the centrosome, MTs undergo rapid transitions through phases of growth, pause and catastrophe, continuously exploring and adapting to the intracellular environment...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28609436/cleavage-of-the-sun-domain-protein-mps3-at-its-n-terminus-regulates-centrosome-disjunction-in-budding-yeast-meiosis
#12
Ping Li, Hui Jin, Bailey A Koch, Rebecca L Abblett, Xuemei Han, John R Yates, Hong-Guo Yu
Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge...
June 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28607478/precocious-centriole-disengagement-and-centrosome-fragmentation-induced-by-mitotic-delay
#13
Menuka Karki, Neda Keyhaninejad, Charles B Shuster
The spindle assembly checkpoint (SAC) delays mitotic progression until all sister chromatid pairs achieve bi-orientation, and while the SAC can maintain mitotic arrest for extended periods, moderate delays in mitotic progression have significant effects on the resulting daughter cells. Here we show that when retinal-pigmented epithelial (RPE1) cells experience mitotic delay, there is a time-dependent increase in centrosome fragmentation and centriole disengagement. While most cells with disengaged centrioles maintain spindle bipolarity, clustering of disengaged centrioles requires the kinesin-14, HSET...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28602627/phosphorylation-of-depdc1-at-ser110-is-required-to-maintain-centrosome-organization-during-mitosis
#14
Dan Chen, Satoko Ito, Toshinori Hyodo, Eri Asano-Inami, Hong Yuan, Takeshi Senga
DEPDC1 (DEP domain containing 1) is overexpressed in multiple cancers and is associated with cell cycle progression. In this report, we have investigated the expression, localization, phosphorylation and function of DEPDC1 during mitosis. DEPDC1 has two isoforms (isoform a and isoform b), and both of them are increased in mitosis and degraded once cells exit mitosis. DEPDC1a is localized to the centrosome in metaphase, whereas DEPDC1b is localized to the entire cell cortex during mitosis. DEPDC1a, but not DEPDC1b, was required for the integrity of centrosome and organization of the bipolar spindle...
June 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28601076/the-centrosome-as-the-main-integrator-of-endothelial-cell-functional-activity
#15
REVIEW
A S Shakhov, I B Alieva
The centrosome is an intracellular structure of the animal cell responsible for organization of cytoplasmic microtubules. According to modern concepts, the centrosome is a very important integral element of the living cell whose functions are not limited to its ability to polymerize microtubules. The centrosome localization in the geometric center of the interphase cell, the high concentration of various regulatory proteins in this area, the centrosome-organized radial system of microtubules for intracellular transport by motor proteins, the centrosome involvement in the perception of external signals and their transmission - all these features make this cellular structure a unique regulation and distribution center managing dynamic morphology of the animal cell...
June 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28600782/dividing-with-extra-centrosomes-a-double-edged-sword-for-cancer-cells
#16
Alexander D Rhys, Susana A Godinho
The presence of supernumerary centrosomes is a hallmark of human tumours. Recent work in animal models suggests that extra centrosomes are not just bystanders in cancer but can accelerate tumourigenesis in the absence of the tumour suppressor p53. Centrosome amplification could indeed actively participate in tumour progression through the induction of chromosome instability, disruption of tissue architecture and promoting cell invasion. Paradoxically, however, centrosome amplification is rather poorly tolerated in normal cells and there are several hurdles cells need to overcome in order to efficiently proliferate in the presence of extra centrosomes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28600781/consequences-of-centrosome-dysfunction-during-brain-development
#17
Maddalena Nano, Renata Basto
Development requires cell proliferation, differentiation and spatial organization of daughter cells to occur in a highly controlled manner. The mode of cell division, the extent of proliferation and the spatial distribution of mitosis allow the formation of tissues of the right size and with the correct structural organization. All these aspects depend on cell cycle duration, correct chromosome segregation and spindle orientation. The centrosome, which is the main microtubule-organizing centre (MTOC) of animal cells, contributes to all these processes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28599311/c-terminal-kinesin-motor-kifc1-participates-in-facilitating-proper-cell-division-of-human-seminoma
#18
Yu-Xi Xiao, Hao-Qing Shen, Zhen-Yu She, Li Sheng, Qian-Qian Chen, Yu-Lan Chu, Fu-Qing Tan, Wan-Xi Yang
C-terminus kinesin motor KIFC1 is known for centrosome clustering in cancer cells with supernumerary centrosomes. KIFC1 crosslinks and glides on microtubules (MT) to assist normal bipolar spindle formation to avoid multi-polar cell division, which might be fatal. Testis cancer is the most common human cancer among young men. However, the gene expression profiles of testis cancer is still not complete and the expression of the C-terminus kinesin motor KIFC1 in testis cancer has not yet been examined. We found that KIFC1 is enriched in seminoma tissues in both mRNA level and protein level, and is specifically enriched in the cells that divide actively...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596487/znf131-suppresses-centrosome-fragmentation-in-glioblastoma-stem-like-cells-through-regulation-of-haus5
#19
Yu Ding, Jacob A Herman, Chad M Toledo, Jackie M Lang, Philip Corrin, Emily J Girard, Ryan Basom, Jeffrey J Delrow, James M Olson, Patrick J Paddison
Zinc finger domain genes comprise ~3% of the human genome, yet many of their functions remain unknown. Here we investigated roles for the vertebrate-specific BTB domain zinc finger gene ZNF131 in the context of human brain tumors. We report that ZNF131 is broadly required for Glioblastoma stem-like cell (GSC) viability, but dispensable for neural progenitor cell (NPC) viability. Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7, NPHP1, and TMEM237, as well as HAUS5, a component of Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595628/six3-a-tumor-suppressor-inhibits-astrocytoma-tumorigenesis-by-transcriptional-repression-of-aurka-b
#20
Zhibin Yu, Yingnan Sun, Xiaoling She, Zeyou Wang, Shuai Chen, Zhiyong Deng, Yan Zhang, Qiang Liu, Qing Liu, Chunhua Zhao, Peiyao Li, Changhong Liu, Jianbo Feng, Haijuan Fu, Guiyuan Li, Minghua Wu
BACKGROUND: SIX homeobox 3 (SIX3) is a member of the sine oculis homeobox transcription factor family. It plays a vital role in the nervous system development. Our previous study showed that the SIX3 gene is hypermethylated, and its expression is decreased in astrocytoma, but the role of SIX3 remains unknown. METHODS: Chromatin-immunoprecipitation (ChIP) and luciferase reporter assay were used to confirm the binding of SIX3 to the promoter regions of aurora kinase A (AURKA) and aurora kinase B (AURKB)...
June 8, 2017: Journal of Hematology & Oncology
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