Centrosome
Centrioles
Spindle Apparatus
Microtubules
Mitosis
Tubulin
Microtubule-Organizing Center
Microtubule-Associated Proteins
Aurora Kinases
Interphase
Aurora Kinase A
Cell Cycle Proteins
Cell Cycle
Chromosomal Instability
Dyneins
Protein-Serine-Threonine Kinases
Nocodazole
Aneuploidy
HeLa Cells
Microscopy, Fluorescence
Prophase
Kinesin
Cell Polarity
Cell Nucleus
Metaphase
Embryo, Nonmammalian
Cilia
Fluorescent Antibody Technique
Kinetochores
Parthenogenesis
Anaphase
RNA Interference
Nuclear Proteins
Genomic Instability
Nuclear Envelope
Cyclin E
Drosophila Proteins
Protein Transport
Cyclin-Dependent Kinase 2
RNA, Small Interfering
Fertilization
Green Fluorescent Proteins
Xenopus Proteins
Polyploidy
Caenorhabditis elegans
Chromosomes
CDC2 Protein Kinase
Caenorhabditis elegans Proteins
Drosophila
Telophase
Cyclin A
Cytoskeletal Proteins
Drosophila melanogaster
Cytoplasm
Recombinant Fusion Proteins
Cell Division
Meiosis
Organoids
Protein Binding
Molecular Sequence Data
Models, Biological
Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. (1/1931)
We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass of 35.9 kDa. C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2, Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis. The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G1/S, accumulates during G2/M, and reduces after mitosis. Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome during mitosis from anaphase to cytokinesis. These results suggest that AIK3 may play a role(s) in centrosome function at later stages of mitosis. (+info)Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers. (2/1931)
The product of the abnormal spindle (asp) gene was found to be an asymmetrically localized component of the centrosome during mitosis, required to focus the poles of the mitotic spindle in vivo. Removing Asp protein function from Drosophila melanogaster embryo extracts, either by mutation or immunodepletion, resulted in loss of their ability to restore microtubule-organizing center activity to salt-stripped centrosome preparations. This was corrected by addition of purified Asp protein. Thus, Asp appears to hold together the microtubule-nucleating gamma-tubulin ring complexes that organize the mitotic centrosome. (+info)Influence of centriole behavior on the first spindle formation in zygotes of the brown alga Fucus distichus (Fucales, Phaeophyceae). (3/1931)
The influence of centrioles, derived from the sperm flagellar basal bodies, and the centrosomal material (MTOCs) on spindle formation in the brown alga Fucus distichus (oogamous) was studied by immunofluorescence microscopy using anti-centrin and anti-beta-tubulin antibodies. In contrast to a bipolar spindle, which is formed after normal fertilization, a multipolar spindle was formed in polyspermic zygote. The number of mitotic poles in polyspermic zygotes was double the number of sperm involved in fertilization. As an anti-centrin staining spot (centrioles) was located at these poles, the multipolar spindles in polyspermic zygotes were produced by the supplementary centrioles. When anucleate egg fragments were fertilized, chromosome condensation and mitosis did not occur in the sperm nucleus. Two anti-centrin staining spots could be detected, microtubules (MTs) radiated from nearby, but the mitotic spindle was never produced. When a single sperm fertilized multinucleate eggs (polygyny), abnormal spindles were also observed. In addition to two mitotic poles containing anti-centrin staining spots, extra mitotic poles without anti-centrin staining spots were also formed, and as a result multipolar spindles were formed. When karyogamy was blocked with colchicine, it became clear that the egg nucleus proceeded independently into mitosis accompanying chromosome condensation. A monoastral spindle could be frequently observed, and in rare cases a barrel-shaped spindle was formed. However, when a sperm nucleus was located near an egg nucleus, the two anti-centrin staining spots shifted to the egg nucleus from the sperm nucleus. In this case, a normal spindle was formed, the egg chromosomes arranged at the equator, and the associated MTs elongated from one pole of the egg spindle toward the sperm chromosomes which were scattered. From these results, it became clear that paternal centrioles derived from the sperm have a crucial role in spindle formation in the brown algae, such as they do during animal fertilization. However, paternal centrioles were not adequate for the functional centrosome during spindle formation. We speculated that centrosomal materials from the egg cytoplasm aggregate around the sperm centrioles and are needed for centrosomal activation. (+info)Tobacco BY-2 cell-free extracts induce the recovery of microtubule nucleating activity of inactivated mammalian centrosomes. (4/1931)
The structure and the molecular composition of the microtubule-organizing centers in acentriolar higher plant cells remain unknown. We developed an in vitro complementation assay where tobacco BY-2 extracts can restore the microtubule-nucleating activity of urea-inactivated mammalian centrosomes. Our results provide first evidence that soluble microtubule-nucleating factors are present in the plant cytosolic fraction. The implication for microtubule nucleation in higher plants is discussed. (+info)Cyclin-dependent kinase control of centrosome duplication. (5/1931)
Centrosomes nucleate microtubules and duplicate once per cell cycle. This duplication and subsequent segregation in mitosis results in maintenance of the one centrosome/cell ratio. Centrosome duplication occurs during the G1/S transition in somatic cells and must be coupled to the events of the nuclear cell cycle; failure to coordinate duplication and mitosis results in abnormal numbers of centrosomes and aberrant mitoses. Using both in vivo and in vitro assays, we show that centrosome duplication in Xenopus laevis embryos requires cyclin/cdk2 kinase activity. Injection of the cdk (cyclin-dependent kinase) inhibitor p21 into one blastomere of a dividing embryo blocks centrosome duplication in that blastomere; the related cdk inhibitor p27 has a similar effect. An in vitro system using Xenopus extracts carries out separation of the paired centrioles within the centrosome. This centriole separation activity is dependent on cyclin/cdk2 activity; depletion of either cdk2 or of the two activating cyclins, cyclin A and cyclin E, eliminates centriole separation activity. In addition, centriole separation is inhibited by the mitotic state, suggesting a mechanism of linking the cell cycle to periodic duplication of the centrosome. (+info)GMAP-210, A cis-Golgi network-associated protein, is a minus end microtubule-binding protein. (6/1931)
We report that a peripheral Golgi protein with a molecular mass of 210 kD localized at the cis-Golgi network (Rios, R.M., A.M. Tassin, C. Celati, C. Antony, M.C. Boissier, J.C. Homberg, and M. Bornens. 1994. J. Cell Biol. 125:997-1013) is a microtubule-binding protein that associates in situ with a subpopulation of stable microtubules. Interaction of this protein, now called GMAP-210, for Golgi microtubule-associated protein 210, with microtubules in vitro is direct, tight and nucleotide-independent. Biochemical analysis further suggests that GMAP-210 specifically binds to microtubule ends. The full-length cDNA encoding GMAP-210 predicts a protein of 1, 979 amino acids with a very long central coiled-coil domain. Deletion analyses in vitro show that the COOH terminus of GMAP-210 binds to microtubules whereas the NH2 terminus binds to Golgi membranes. Overexpression of GMAP-210-encoding cDNA induced a dramatic enlargement of the Golgi apparatus and perturbations in the microtubule network. These effects did not occur when a mutant lacking the COOH-terminal domain was expressed. When transfected in fusion with the green fluorescent protein, the NH2-terminal domain associated with the cis-Golgi network whereas the COOH-terminal microtubule-binding domain localized at the centrosome. Altogether these data support the view that GMAP-210 serves to link the cis-Golgi network to the minus ends of centrosome-nucleated microtubules. In addition, this interaction appears essential for ensuring the proper morphology and size of the Golgi apparatus. (+info)HP33: hepatocellular carcinoma-enriched 33-kDa protein with similarity to mitochondrial N-acyltransferase but localized in a microtubule-dependent manner at the centrosome. (7/1931)
Using a new subtraction method and chemically induced rat hepatocellular carcinomas, we identified a hepatocellular carcinogenesis and hepatocyte proliferation-related gene designated hp33 that encoded a 33-kDa protein. The predicted protein was similar to the bovine aralkyl N-acyltransferase and arylacetyl N-acyltransferase. HP33 was restrictively expressed in the liver and kidney, and its gene expression was stimulated in the regenerating liver as well as in hepatocellular carcinoma. Interestingly, it was demonstrated in various hepatic cells that HP33 was localized in regions surrounding the centrosome, where mitochondria were not concentrated. Moreover, its centrosomal localization was evident in the interphase but not in the mitotic phase of the cell cycle. The centrosomal localization of HP33 was dependent on microtubules, and ectopically expressed HP33 was seen at centrosomes even in fibroblasts, which do not exhibit a typical staining pattern of HP33. The centrosomal localization of HP33 became invisible by nocodazole treatment, whereas the mitochondrial staining pattern was not affected by it. In vitro cosedimentation experiments using purified microtubules indicated that HP33 bound to MTs directly and that its MT-binding ability was dependent on the C-terminal basic domain of the protein. These results suggest that, different from early predictions based on its primary structure, HP33 has a growth- and carcinogenesis-related function that may be independent of mitochondrial function. (+info)Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. (8/1931)
Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G2-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis. (+info)Causes of Chromosomal Instability:
1. Genetic mutations: Mutations in genes that regulate the cell cycle or chromosome segregation can lead to CIN.
2. Environmental factors: Exposure to certain environmental agents such as radiation and certain chemicals can increase the risk of developing CIN.
3. Errors during DNA replication: Mistakes during DNA replication can also lead to CIN.
Types of Chromosomal Instability:
1. Aneuploidy: Cells with an abnormal number of chromosomes, either more or fewer than the normal diploid number (46 in humans).
2. Structural changes: Deletions, duplications, inversions, translocations, and other structural changes can occur in the chromosomes.
3. Unstable chromosome structures: Chromosomes with abnormal shapes or structures, such as telomere shortening, centromere instability, or chromosome breaks, can also lead to CIN.
Effects of Chromosomal Instability:
1. Cancer: CIN can increase the risk of developing cancer by disrupting normal cellular processes and leading to genetic mutations.
2. Aging: CIN can contribute to aging by shortening telomeres, which are the protective caps at the ends of chromosomes that help maintain their stability.
3. Neurodegenerative diseases: CIN has been implicated in the development of certain neurodegenerative diseases such as Alzheimer's and Parkinson's.
4. Infertility: CIN can lead to infertility by disrupting normal meiotic recombination and chromosome segregation during gametogenesis.
Detection and Diagnosis of Chromosomal Instability:
1. Karyotyping: This is a technique used to visualize the entire set of chromosomes in a cell. It can help identify structural abnormalities such as deletions, duplications, or translocations.
2. Fluorescence in situ hybridization (FISH): This technique uses fluorescent probes to detect specific DNA sequences or proteins on chromosomes. It can help identify changes in chromosome structure or number.
3. Array comparative genomic hybridization (aCGH): This technique compares the genetic material of a sample to a reference genome to identify copy number changes.
4. Next-generation sequencing (NGS): This technique can identify point mutations and other genetic changes in DNA.
Treatment and Management of Chromosomal Instability:
1. Cancer treatment: Depending on the type and stage of cancer, treatments such as chemotherapy, radiation therapy, or surgery may be used to eliminate cancer cells with CIN.
2. Prenatal testing: Pregnant women with a family history of CIN can undergo prenatal testing to detect chromosomal abnormalities in their fetuses.
3. Genetic counseling: Individuals with a family history of CIN can consult with a genetic counselor to discuss risk factors and potential testing options.
4. Lifestyle modifications: Making healthy lifestyle choices such as maintaining a balanced diet, exercising regularly, and not smoking can help reduce the risk of developing cancer and other diseases associated with CIN.
In conclusion, chromosomal instability is a common feature of many human diseases, including cancer, and can be caused by a variety of factors. The diagnosis and management of CIN require a multidisciplinary approach that includes cytogenetic analysis, molecular diagnostics, and clinical evaluation. Understanding the causes and consequences of CIN is crucial for developing effective therapies and improving patient outcomes.
There are several types of aneuploidy, including:
1. Trisomy: This is the presence of an extra copy of a chromosome. For example, Down syndrome is caused by an extra copy of chromosome 21 (trisomy 21).
2. Monosomy: This is the absence of a chromosome.
3. Mosaicism: This is the presence of both normal and abnormal cells in the body.
4. Uniparental disomy: This is the presence of two copies of a chromosome from one parent, rather than one copy each from both parents.
Aneuploidy can occur due to various factors such as errors during cell division, exposure to certain chemicals or radiation, or inheritance of an abnormal number of chromosomes from one's parents. The risk of aneuploidy increases with age, especially for women over the age of 35, as their eggs are more prone to errors during meiosis (the process by which egg cells are produced).
Aneuploidy can be diagnosed through various methods such as karyotyping (examining chromosomes under a microscope), fluorescence in situ hybridization (FISH) or quantitative PCR. Treatment for aneuploidy depends on the underlying cause and the specific health problems it has caused. In some cases, treatment may involve managing symptoms, while in others, it may involve correcting the genetic abnormality itself.
In summary, aneuploidy is a condition where there is an abnormal number of chromosomes present in a cell, which can lead to various developmental and health problems. It can occur due to various factors and can be diagnosed through different methods. Treatment depends on the underlying cause and the specific health problems it has caused.
There are several types of genomic instability, including:
1. Chromosomal instability (CIN): This refers to changes in the number or structure of chromosomes, such as aneuploidy (having an abnormal number of chromosomes) or translocations (the movement of genetic material between chromosomes).
2. Point mutations: These are changes in a single base pair in the DNA sequence.
3. Insertions and deletions: These are changes in the number of base pairs in the DNA sequence, resulting in the insertion or deletion of one or more base pairs.
4. Genomic rearrangements: These are changes in the structure of the genome, such as chromosomal breaks and reunions, or the movement of genetic material between chromosomes.
Genomic instability can arise from a variety of sources, including environmental factors, errors during DNA replication and repair, and genetic mutations. It is often associated with cancer, as cancer cells have high levels of genomic instability, which can lead to the development of resistance to chemotherapy and radiation therapy.
Research into genomic instability has led to a greater understanding of the mechanisms underlying cancer and other diseases, and has also spurred the development of new therapeutic strategies, such as targeted therapies and immunotherapies.
In summary, genomic instability is a key feature of cancer cells and is associated with various diseases, including cancer, neurodegenerative disorders, and aging. It can arise from a variety of sources and is the subject of ongoing research in the field of molecular biology.
Polyploidy is a condition where an organism has more than two sets of chromosomes, which are the thread-like structures that carry genetic information. It can occur in both plants and animals, although it is relatively rare in most species. In humans, polyploidy is extremely rare and usually occurs as a result of errors during cell division or abnormal fertilization.
In medicine, polyploidy is often used to describe certain types of cancer, such as breast cancer or colon cancer, that have extra sets of chromosomes. This can lead to the development of more aggressive and difficult-to-treat tumors.
However, not all cases of polyploidy are cancerous. Some individuals with Down syndrome, for example, have an extra copy of chromosome 21, which is a non-cancerous form of polyploidy. Additionally, some people may be born with extra copies of certain genes or chromosomal regions due to errors during embryonic development, which can lead to various health problems but are not cancerous.
Overall, the term "polyploidy" in medicine is used to describe any condition where an organism has more than two sets of chromosomes, regardless of whether it is cancerous or non-cancerous.
Centrosome
Centrosome cycle
Alms1, centrosome and basal body associated protein
KIF15
Renata Basto
List of German inventors and discoverers
Katharine Foot
Ninein-like protein
ADP-ribosylation
Centriole
Mónica Bettencourt-Dias
Glossary of engineering: A-L
Feline foamy virus
CEP68
Spindle apparatus
Cytoskeleton
Actomyosin ring
PCM1
Oogenesis
STK38
HERC2
BRSK1
USP9X
Spindle checkpoint
Multipolar spindles
SSX2IP
RANBP1
TUBG1
C20orf27
CEP192
Centrosomes - LC Linked Data Service: Authorities and Vocabularies | Library of Congress
Activation of maternal centrosomes in unfertilized sea urchin eggs - NASA Technical Reports Server (NTRS)
Identification of novel small molecule inhibitors of centrosome clustering in cancer cells - Lancaster EPrints
YRC Public Data Repository - Gene Ontology - positive regulation of centrosome cycle
Cell cycle dependent regulation of centrosome maturation by Drosophila Pericentrin | NIH Research Festival
Dynamic Recruitment of CDK5RAP2 to Centrosomes Requires Its Association with Dynein - Fingerprint - Northwestern Scholars
Reactome | Recruitment of NuMA to mitotic centrosomes
Microtubule release from the centrosome in migrating cells - UEA Digital Repository
SSNH3ANA
BAP1-inactivated melanocytic tumors show prominent centrosome amplification and associated loss of primary cilia. | J Cutan...
Cell Structure and Function - Vocabulary - Course Hero
SP-4: Centrosome integrity as a determinant of replication stress and mitotic dysfunction - FOR-2800
High-content screening and profiling of drug activity in an automated centrosome-duplication assay :: MPG.PuRe
Lats1 suppresses centrosome overduplication by modulating the stability of Cdc25B.下载|翻译|阅读
"Centrosome-dependent microtubule modifications set the conditions for " by Durga Praveen Meka, Ewelina Betleja et al.
Microtubule nucleation around the centrosome as well as the fungal equal - Outlook on PI3K/AKT/mTOR inhibition
Cell Division II | Biology | Visionlearning
Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement. - Department of Physiology,...
A USP28-53BP1-p53-p21 signaling axis arrests growth after centrosome loss or prolonged mitosis<...
The centriole is a multifunctional structure that organizes centrosomes and cilia - nhibition of Hepatitis C Virus Replication
Super-resolution microscopy demystified | Nature Cell Biology
Eukaryotic Cells
Fhod1 formin homology 2 domain containing 1 [Mus musculus (house mouse)] - Gene - NCBI
The Meng-Fu Bryan Tsou Lab | Sloan Kettering Institute
Zentrosoma - Wikipedia, entziklopedia askea.
JoVE Science Education > Cell...
Cutaneous Malignancies Unit | NIAMS
Cystic Diseases of the Kidney: Practice Essentials, Pathophysiology, Etiology
Centrioles6
- Centrosomes consist of a pair of centrioles encircled by pericentriolar material (PCM). (nih.gov)
- Centrosome maturation is a key cell cycle-dependent process that facilitates recruitment of PCM proteins to the centrioles thereby enabling centrosome-driven functions, including microtubule nucleation. (nih.gov)
- Pericentrin like protein (Plp) is a radially organized centrosome linker protein that bridges centrioles and PCM. (nih.gov)
- 2015). The animal centrosome is composed by two centrioles surrounded by a protein-rich material, the pericentriolar matrix (PCM). (pkc-inhibitor.com)
- The goal of my research is to understand the biogenesis of centrioles/centrosomes and primary cilia, and how defects in these processes affect mammalian cell physiology and evoke stress responses. (mskcc.org)
- A centrosome has two cylindrical centrioles at its core. (jove.com)
Microtubule8
- Centrosomes are undetectable in unfertilized sea urchin eggs, and normally the sperm introduces the cell's microtubule-organizing center (MTOC) at fertilization. (nasa.gov)
- However, artificial activation or parthenogenesis triggers microtubule assembly in the unfertilized egg, and this study explores the reappearance and behavior of the maternal centrosome. (nasa.gov)
- Later, the centrosome becomes more distinct and organizes a radial microtubule shell, and eventually a compact centrosome at the egg center organizes a monaster. (nasa.gov)
- Centrosomes are the major microtubule organizing centers in most eukaryotic cells. (nih.gov)
- Centrosome-dependent microtubule modifications set the conditions for " by Durga Praveen Meka, Ewelina Betleja et al. (wustl.edu)
- Microtubule nucleation around the centrosome as well as the fungal equal the spindle pole body (SPB) is activated on the starting point of mitosis. (gasyblog.com)
- The primary microtubule organizing center (MTOC) in animal cells is the centrosome. (jove.com)
- During interphase, the centrosome nucleates microtubule outgrowth. (bvsalud.org)
Mitosis7
- Most normal cells have two centrosomes that form bipolar spindles during mitosis, while cancer cells often contain more than two, or "supernumerary" centrosomes. (lancs.ac.uk)
- That is, in interphase Plp resides in a inhibited conformation that prevent PCM recruitment, and in mitosis, Polo relieves Plp from autoinhibition that in turn allows interaction with PCM components thereby activating centrosomes to nucleate microtubules. (nih.gov)
- Centrosomes are crucial in the assembly of mitotic spindles and faithful separation of chromosomes in mitosis. (for2800.de)
- Moreover, in cooperation with Holger Bastians (SP2), we will test whether this replication stress upon centrosome disruption also contributes to spindle abnormalities, chromosome missegregation in the subsequent mitosis. (for2800.de)
- Moreover, detailed analyses of structural and numerical chromosome aberrations in response to centrosome disruption will be performed together with SP-Z. Finally, we will ask whether centrosomal abnormalities also affect the characteristics of how under-replicated DNA is repaired during mitosis. (for2800.de)
- We therefore propose that centrosome loss or a prolonged mitosis activate a common signaling pathway that acts to prevent the growth of cells that have an increased propensity for mitotic errors. (johnshopkins.edu)
- The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS). (bvsalud.org)
Microtubules3
- NuMA is transported to the mitotic poles where it forms an insoluble crescent around centrosomes tethering microtubules into the bipolar configuration of the mitotic apparatus (Merdes et al. (reactome.org)
- Although NuMA is not a bona fide constituent of the mitotic centrosome but rather a protein associated with microtubules at the spindle pole, specific splice variants of NuMA have been identified that associate with the centrosome during interphase (Tang et al, 1994). (reactome.org)
- Nanotube s were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 µg/cm2 SWCNT. (cdc.gov)
Interphase2
- Taken together, these data suggest that Lats1 regulates Cdc25B protein level and subsequent Cdk2 activity, thereby suppressing centrosome overduplication during interphase. (shengsci.com)
- In interphase, centrosomes and their anchored MTs regulate the placing of many molecules and structures such as nuclei and the Golgi along with the stability of cellular junctions and adhesions, helping to define cell form and polarity (Akhmanova et al. (pkc-inhibitor.com)
Response to centrosome1
- However, the mechanism by which p53 is activated in response to centrosome loss remains unknown. (johnshopkins.edu)
Regulation of centrosome1
- Precise regulation of centrosome number is critical for accurate chromosome segregation and the maintenance of genomic integrity. (johnshopkins.edu)
Mitotic centrosomes1
- The PTEN-Akt pathway impacts the integrity and composition of mitotic centrosomes. (nih.gov)
Proteins3
- The Lats proteins localize at centrosomes, but their centrosomal functions remain elusive. (shengsci.com)
- Pathogenic LRRK2 does not displace proteinaceous linker proteins which hold duplicated centrosomes together, but causes the centrosomal displacement of CDK5RAP2, a protein critical for centrosome cohesion. (ox.ac.uk)
- The LRRK2-mediated centrosomal displacement of CDK5RAP2 requires RILPL1 and phospho-Rab proteins, which stably associate with centrosomes. (ox.ac.uk)
Cilia8
- BAP1-inactivated melanocytic tumors show prominent centrosome amplification and associated loss of primary cilia. (bvsalud.org)
- Because the primary cilium is nucleated on the mother centriole , we examined the connection between the presence of primary cilia and the formation of centrosomes in BAP1-inactivated melanocytic tumors (BIMTs). (bvsalud.org)
- We evaluated the cilia and centrosomes in 11 BIMTs and five conventional melanocytic nevi using immunofluorescence staining of acetylated alpha-tubulin and gamma-tubulin . (bvsalud.org)
- We found that, compared to nevi , BIMTs show loss of primary cilia and amplification of centrosomes . (bvsalud.org)
- Although centrosome amplification does not absolutely correlate with loss of primary cilia in melanocytic neoplasms , absence of BAP1 exacerbates the phenotype . (bvsalud.org)
- Moreover, aberrant centrosome and cilia formation are likely critical in the pathogenesis of other BAP1-inactivated tumors . (bvsalud.org)
- The centriole is a multifunctional structure that organizes centrosomes and cilia and is important for cell signaling, cell cycle progression, polarity, and motility. (pkc-inhibitor.com)
- Cell biologist Meng-Fu Bryan Tsou studies cell cycle control of centrosome duplication and degeneration, as well as cilia assembly and disassembly. (mskcc.org)
Regulates3
- We also found that Lats1 physically interacts with Cdc25B phosphatase that localizes both at the centrosome and in the nucleus and regulates the linkage between the centrosome cycle and mitotic progression. (shengsci.com)
- Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement. (ox.ac.uk)
- Centrosome anchoring regulates progenitor properties and cortical formation. (mskcc.org)
Protein1
- To investigate the precise role of Plp during centrosome maturation, we performed a structure-function analysis by generating Plp protein truncation and characterized its function in vivo. (nih.gov)
Centrosomal2
- At fertilization, paternal centrosomes become dominant over the maternal centrosomal material. (nasa.gov)
- Preliminary results indicate that the disruption of centrosomes, by inhibiting polo-like kinase 4 (PLK4) or by depletion of centrosomal components, hinders the progression of DNA replication forks. (for2800.de)
Chromosome missegregation2
- Numerical aberration of the centrosome results in chromosome missegregation, eventually leading to chromosomal instability, a hallmark of human tumor malignancy. (shengsci.com)
- In Lats1(-/-) MEFs, centrosomes were markedly overduplicated, leading to severe mitotic defects such as chromosome missegregation and cytokinesis failure. (shengsci.com)
Pericentriolar1
- Centro celular que consiste en un par de CENTRIOLOS rodeados por una nube de material amorfo llamada región pericentriolar. (bvsalud.org)
Disruption3
- In conclusion, the disruption of centrosomes activates MK2 and impairs DNA replication fork progression. (for2800.de)
- This includes the identification of signaling pathways that are induced by centrosome disruption and that lead to impaired DNA replication. (for2800.de)
- Disruption of the centrosome is common in many solid tumors including lung cancer. (cdc.gov)
Duplication1
- Centrosome framework and centriole duplication routine in vertebrates. (pkc-inhibitor.com)
Kinase1
- By performing in vivo mass spectrometric analysis on these regulatory regions, we identified the precise phosphorylation sites that are targeted by Polo, which is a key kinase of centrosome maturation. (nih.gov)
Poles1
- Such cancer cells achieve bipolar division by clustering their centrosomes into two functional poles, and inhibiting this process then leads to cancer-specific cell death. (lancs.ac.uk)
Centriole1
- PPP1R35 ensures centriole homeostasis by promoting centriole-to-centrosome conversion. (mskcc.org)
Ciliogenesis2
- The phospho-Rab/RILPL1 interaction causes deficits in ciliogenesis and interferes with the cohesion of duplicated centrosomes. (ox.ac.uk)
- Using quantitative proteomics, super-resolution microscopy, comparative genomics, proximity labeling, and whole genome CRISPR screen, we have identified lists of new components associated with vertebrate centrosomes and ciliogenesis. (mskcc.org)
Cells2
- To discover new compounds with greater specificity for cancer cells, we established a high-content screen for agents that block centrosome clustering in BT-549 cells, a breast cancer cell line that harbors supernumerary centrosomes. (lancs.ac.uk)
- In nontransformed cells, centrosome loss triggers a p53-dependent surveillance pathway that protects against genome instability by blocking cell growth. (johnshopkins.edu)
Pathways1
- Since centrosome clustering is a complex process involving multiple pathways, the 14 compounds identified in this study provide a potentially novel means to developing non-cross-resistant anti-cancer drugs that block centrosome clustering. (lancs.ac.uk)
Defects1
- Lkb1-deficient HSCs, but not AMPK-deficient HSCs, exhibited defects in centrosomes and mitotic spindles in culture, and became aneuploid. (nih.gov)
Pathway1
- Here, we have used genome-wide CRI SPR/Cas9 knockout screens to identify a USP28-53BP1-p53-p21 signaling axis at the core of the centrosome surveillance pathway. (johnshopkins.edu)
Aneuploid1
- We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. (cdc.gov)
Precise1
- One of these compounds, N2-(3-pyridylmethyl)-5-nitro-2-furamide (Centrosome Clustering Chemical Inhibitor-01, CCCI-01), that showed the greatest differential response in this screen was confirmed to have selective effects on cancer as compared to normal breast progenitors using more precise apoptosis induction and clonogenic growth endpoints. (lancs.ac.uk)
Cell cycle1
- Like chromosomes, centrosomes need to be duplicated exactly once during the cell cycle, suggesting mutual regulation. (for2800.de)
Structural1
- Some of these compounds were structurally similar, suggesting a common structural motif important for preventing centrosome clustering. (lancs.ac.uk)
Structure1
- Three-dimensional reconstructions showed carbon nanotube s within the centrosome structure. (cdc.gov)
Show1
- We show that USP28 and 53BP1 act to stabilize p53 after centrosome loss and demonstrate this function to be independent of their previously characterized role in the DNA damage response. (johnshopkins.edu)
Cycle1
- Any process that activates or increases the frequency, rate or extent of the centrosome cycle. (yeastrc.org)
Important1
- The centrosome is an important MT-nucleating and signaling center of the cell (Arquint et al. (pkc-inhibitor.com)
Study1
- Drosophila is an excellent model system to study the centrosome and diseases that are related to their dysfunction. (nih.gov)
Formation1
- Additionally, studies have revealed roles for BAP1 in centrosome and mitotic spindle formation. (bvsalud.org)