The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries
Erich A. Nigg,Tim Stearns +1 more
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TLDR
The spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of Centrosomes and centrosomes are discussed.Abstract:
Centrosomes are microtubule-organizing centres of animal cells. They influence the morphology of the microtubule cytoskeleton, function as the base for the primary cilium and serve as a nexus for important signalling pathways. At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated pericentriolar material. Cells begin the cell cycle with exactly one centrosome, and the duplication of centrioles is constrained such that it occurs only once per cell cycle and at a specific site in the cell. As a result of this duplication mechanism, the two centrioles differ in age and maturity, and thus have different functions; for example, the older of the two centrioles can initiate the formation of a ciliary axoneme. We discuss spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of centrioles and centrosomes.read more
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Polo‐like kinase 4 inhibitor CFI‐400945 suppresses liver cancer through cell cycle perturbation and eliciting antitumor immunity
Cerise Yuen-Ki Chan,Vincent Wai-Hin Yuen,David Kung-Chun Chiu,Chi Ching Goh,Kelsie L. Thu,David W. Cescon,Isabel Soria-Bretones,Cheuk-Ting Law,Jacinth Wing-Sum Cheu,Derek Lee,Aki Pui-Wah Tse,Kel Vin Tan,Misty Shuo Zhang,Bowie Wong,Chun-Ming Wong,Pek-Lan Khong,Irene Oi-Lin Ng,Mark R. Bray,Tak W. Mak,Thomas Yau,Carmen Chak-Lui Wong +20 more
TL;DR: It is shown that by targeting a centrosome regulator, PLK4, to activate the cytosolic DNA sensing-mediated immune response, CFI-400945 effectively restrained tumor progression through cell cycle inhibition and inducing anti-tumor immunity to achieve a durable suppressive effect even in late-staged mouse HCC.
Journal ArticleDOI
Identification of a Structurally Dynamic Domain for Oligomer Formation in Rootletin.
TL;DR: The coiled-coil domain 3 (CCD3) of rootletin is identified as the key domain for its cellular function and it is shown that oligomerization-defective CCD3 mutants fail in centrosomal localization and centriole linker connecting the two mother centrioles.
Book ChapterDOI
Parthenogenesis in Insects: The Centriole Renaissance
TL;DR: Here, attention is focused on the assembly of functional centrosomes following fertilization and during parthenogenetic development in insects, a useful experimental system to investigate centriole assembly and duplication together with centrosome formation and maturation.
Journal ArticleDOI
Centrosomes are required for proper β-catenin processing and Wnt response
TL;DR: A pool of β-catenin effectively shielded from regulation by Wnt is identified, and a model whereby centrosomes prevent inappropriate β- catenin modifications that antagonize normal stabilization by WNT signals is presented.
Journal ArticleDOI
Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
Tereza Renzova,Dáša Bohačiaková,Milan Ešner,Milan Ešner,Veronika Pospíšilová,Tomáš Bárta,Aleš Hampl,Lukas Cajanek +7 more
TL;DR: It is demonstrated that blocking of PLK4 or STIL functions leads to centrosome loss followed by both p53-dependent and -independent defects, including prolonged cell divisions, upregulation of p53, chromosome instability, and, importantly, reduction of pluripotency markers and induction of differentiation.
References
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The primary cilium: a signalling centre during vertebrate development
TL;DR: The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction, and the cilium represents a nexus for signalling pathways during development.
Journal ArticleDOI
A Mechanism Linking Extra Centrosomes to Chromosomal Instability
TL;DR: It is demonstrated that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable, and it is proposed that this mechanism may be a common underlying cause of CIN in human cancer.
Journal ArticleDOI
Proteomic characterization of the human centrosome by protein correlation profiling
Jens S. Andersen,Christopher J. Wilkinson,Thibault Mayor,Thibault Mayor,Peter Mortensen,Erich A. Nigg,Matthias Mann +6 more
TL;DR: A mass-spectrometry-based proteomic analysis of human centrosomes in the interphase of the cell cycle by quantitatively profiling hundreds of proteins across several centrifugation fractions identified and validated 23 novel components and identified 41 likely candidates as well as the vast majority of the known centrosomal proteins in a large background of nonspecific proteins.
Journal ArticleDOI
Hippo signaling: growth control and beyond
Georg Halder,Randy L. Johnson +1 more
TL;DR: Recently discovered mechanisms that contribute to the dynamic regulation of Hippo signaling during Drosophila and vertebrate development are reviewed and exciting new insights are provided into the elusive mechanisms that regulate organ growth and regeneration.
Journal ArticleDOI
Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast
TL;DR: It is shown here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro and depends on a conserved protein called separin for sister chromatid separation.