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https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#1
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#2
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28904333/the-ino80-complex-mediates-epigenetic-centromere-propagation-via-active-removal-of-histone-h3
#3
Eun Shik Choi, Youngseo Cheon, Keunsoo Kang, Daeyoup Lee
The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-A(Cnp1) chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1(Hrp1)...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28857608/proteomic-alterations-of-fibroblasts-induced-by-ovarian-cancer-cells-reveal-potential-cancer-targets
#4
X Y Zhang, S S Hong, M Zhang, Q Q Cai, M X Zhang, C J Xu
The common spread pattern of ovarian cancer is peritoneal implantation. The growth of the shed ovarian cancer cells in the peritoneal cavity is closely related to the tumor microenvironment. Cancer-associated fibroblasts are vital in the tumor microenvironment. It is not clearly defined that the protein expression alters during the activating process of fibroblasts. This study detected the protein alterations in fibroblasts induced by ovarian cancer cells and explored the potential biological relevance through two-dimensional gel electrophoresis and mass spectrometry...
August 31, 2017: Neoplasma
https://www.readbyqxmd.com/read/28840245/centromere-dynamics-in-male-and-female-germ-cells
#5
Elaine M Dunleavy, Caitríona M Collins
In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide asymmetrically to generate gonial pre-cursors, which are amplified in number by mitotic divisions, undergo meiosis and eventually differentiate into mature gametes (haploid eggs and sperm). Information transmitted with gametes is inherited by offspring, and potentially by subsequent generations, instructing in organismal development and beyond. Meiosis comprises one round of DNA replication, followed by two rounds of chromosome segregation; homologous chromosomes segregate in the first division (meiosis I) and sister chromatids segregate in the second division (meiosis II)...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840243/dna-sequences-in-centromere-formation-and-function
#6
M Dumont, D Fachinetti
Faithful chromosome segregation during cell division depends on the centromere, a complex DNA/protein structure that links chromosomes to spindle microtubules. This chromosomal domain has to be marked throughout cell division and its chromosomal localization preserved across cell generations. From fission yeast to human, centromeres are established on a series of repetitive DNA sequences and on specialized centromeric chromatin. This chromatin is enriched with the histone H3 variant, named CENP-A, that was demonstrated to be the epigenetic mark that maintains centromere identity and function indefinitely...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840239/post-translational-modifications-of-centromeric-chromatin
#7
Ana García Del Arco, Sylvia Erhardt
Regulation of chromatin structures is important for the control of DNA processes such as gene expression, and misregulation of chromatin is implicated in diverse diseases. Covalent post-translational modifications of histones are a prominent way to regulate chromatin structure and different chromatin regions bear their specific signature of histone modifications. The composition of centromeric chromatin is significantly different from other chromatin structures and mainly defined by the presence of the histone H3-variant CENP-A...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840238/artificial-chromosomes-and-strategies-to-initiate-epigenetic-centromere-establishment
#8
Evelyne J Barrey, Patrick Heun
In recent years, various synthetic approaches have been developed to address the question of what directs centromere establishment and maintenance. In this chapter, we will discuss how approaches aimed at constructing synthetic centromeres have co-evolved with and contributed to shape the theory describing the determinants of centromere identity. We will first review lessons learned from artificial chromosomes created from "naked" centromeric sequences to investigate the role of the underlying DNA for centromere formation...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840237/orchestrating-the-specific-assembly-of-centromeric-nucleosomes
#9
Ewelina Zasadzińska, Daniel R Foltz
Centromeres are chromosomal loci that are defined epigenetically in most eukaryotes by incorporation of a centromere-specific nucleosome in which the canonical histone H3 variant is replaced by Centromere Protein A (CENP-A). Therefore, the assembly and propagation of centromeric nucleosomes are critical for maintaining centromere identify and ensuring genomic stability. Centromeres direct chromosome segregation (during mitosis and meiosis) by recruiting the constitutive centromere-associated network of proteins throughout the cell cycle that in turn recruits the kinetochore during mitosis...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840236/quantitative-microscopy-reveals-centromeric-chromatin-stability-size-and-cell-cycle-mechanisms-to-maintain-centromere-homeostasis
#10
Ana Stankovic, Lars E T Jansen
Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28827290/kinetochore-components-required-for-centromeric-chromatin-assembly-are-impacted-by-msc1-in-schizosaccharomyces-pombe
#11
Chenchao Gao, Lauren Langbein, Fariha Kamal, Anuja A George, Nancy C Walworth
Eukaryotic chromosome segregation requires a protein complex known as the kinetochore that mediates attachment between mitotic spindle microtubules and centromere-specific nucleosomes composed of the widely conserved histone variant CENP-A. Mutations in kinetochore proteins of the fission yeast Schizosaccharomyces pombe lead to chromosome missegregation such that daughter cells emerge from mitosis with unequal DNA content. We find that multiple copies of Msc1, a fission yeast homologue of the KDM5 family of proteins, suppresses the temperature-sensitive growth defect of several kinetochore mutants, including mis16 and mis18, as well as mis6, mis15 and mis17, components of the Constitutive Centromere Associated Network (CCAN)...
August 21, 2017: Genetics
https://www.readbyqxmd.com/read/28819432/silencing-of-hjurp-induces-dysregulation-of-cell-cycle-and-ros-metabolism-in-bladder-cancer-cells-via-ppar%C3%AE-sirt1-feedback-loop
#12
Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Guofeng Qian, Conghua Xie, Han C Dan, Wei Jiang, Min Wu, Chin-Lee Wu, Yu Xiao, Xinghuan Wang
Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819127/multiple-e3s-promote-the-degradation-of-histone-h3-variant-cse4
#13
Haili Cheng, Xin Bao, Xin Gan, Shiwen Luo, Hai Rao
The histone H3-like protein Cse4/CENP-A acts as a key molecular marker that differentiates the special centromeric chromatin structures from bulk nucleosomes. As altered Cse4/CENP-A activity leads to genome instability, it is pivotal to understand the mechanism underlying Cse4 regulation. Here, we demonstrate that four ubiquitin ligases (i.e., Ubr1, Slx5, Psh1, and Rcy1) work in parallel to promote Cse4 turnover in yeast. Interestingly, Cse4 overexpression leads to cellular toxicity and cell cycle delay in yeast cells lacking PSH1, but not in cells lacking UBR1, suggesting different roles of these two degradation pathways...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816574/sgt1-hsp90-complex-is-required-for-cenp-a-deposition-at-centromeres
#14
Yohei Niikura, Risa Kitagawa, Hiroo Ogi, Katsumi Kitagawa
The centromere plays an essential role in accurate chromosome segregation, and defects in its function lead to aneuploidy and thus cancer. The centromere-specific histone H3 variant CENP-A is proposed to be the epigenetic mark of the centromere, as active centromeres require CENP-A-containing nucleosomes to direct the recruitment of multiple kinetochore proteins. CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. However, the mechanism that controls the E3 ligase activity of the CUL4A-RBX1-COPS8 complex remains obscure...
September 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28805800/optogenetic-control-of-kinetochore-function
#15
Huaiying Zhang, Chanat Aonbangkhen, Ekaterina V Tarasovetc, Edward R Ballister, David M Chenoweth, Michael A Lampson
Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools that can manipulate kinetochores on biologically relevant temporal and spatial scales. Optogenetic approaches have the potential to provide temporal and spatial control with molecular specificity...
October 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28795467/cenp-r-acts-bilaterally-as-a-tumor-suppressor-and-an-oncogene-in-the-two-stage-skin-carcinogenesis-model
#16
Kazuhiro Okumura, Naoko Kagawa, Megumi Saito, Yasuhiro Yoshizawa, Haruka Munakata, Eriko Isogai, Tatsuo Fukagawa, Yuichi Wakabayashi
CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R deficient chicken DT40 cells are viable and show very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R deficient mice (Cenp-r(-/-) ). Mice heterozygous or homozygous for Cenp-r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp-r is not essential for normal development...
August 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28791511/centromere-inheritance-through-the-germline
#17
REVIEW
Arunika Das, Evan M Smoak, Ricardo Linares-Saldana, Michael A Lampson, Ben E Black
The centromere directs chromosome segregation and genetic inheritance but is not itself heritable in a canonical, DNA-based manner. In most species, centromeres are epigenetically defined by the presence of a histone H3 variant centromere protein A (CENP-A), independent of underlying DNA sequence. Therefore, centromere inheritance depends on maintaining the CENP-A nucleosome mark across generations. Experiments in cycling somatic cells have led to a model in which centromere identity is maintained by a cell cycle-coupled CENP-A chromatin assembly pathway...
August 8, 2017: Chromosoma
https://www.readbyqxmd.com/read/28760857/fbw7-loss-promotes-chromosomal-instability-and-tumorigenesis-via-cyclin-e1-cdk2-mediated-phosphorylation-of-cenp-a
#18
Mamoru Takada, Weiguo Zhang, Aussie Suzuki, Taruho S Kuroda, Zhouliang Yu, Hiroyuki Inuzuka, Daming Gao, Lixin Wan, Ming Zhuang, Lianxin Hu, Bo Zhai, Christopher J Fry, Kerry Bloom, Guohong Li, Gary H Karpen, Wenyi Wei, Qing Zhang
The centromere regulates proper chromosome segregation, and its dysfunction is implicated in chromosomal instability (CIN). However, relatively little is known about how centromere dysfunction occurs in cancer. Here, we define the consequences of phosphorylation by cyclin E1/CDK2 on a conserved Ser18 residue of centromere-associated protein CENP-A, an essential histone H3 variant that specifies centromere identity. Ser18 hyperphosphorylation in cells occurred upon loss of FBW7, a tumor suppressor whose inactivation leads to CIN...
July 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28756949/expanded-satellite-repeats-amplify-a-discrete-cenp-a-nucleosome-assembly-site-on-chromosomes-that-drive-in-female-meiosis
#19
Aiko Iwata-Otsubo, Jennine M Dawicki-McKenna, Takashi Akera, Samantha J Falk, Lukáš Chmátal, Karren Yang, Beth A Sullivan, Richard M Schultz, Michael A Lampson, Ben E Black
Female meiosis provides an opportunity for selfish genetic elements to violate Mendel's law of segregation by increasing the chance of segregating to the egg [1]. Centromeres and other repetitive sequences can drive in meiosis by cheating the segregation process [2], but the underlying mechanisms are unknown. Here, we show that centromeres with more satellite repeats house more nucleosomes that confer centromere identity, containing the histone H3 variant CENP-A, and bias their segregation to the egg relative to centromeres with fewer repeats...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28754846/overexpression-of-the-e2f-target-gene-cenpi-promotes-chromosome-instability-and-predicts-poor-prognosis-in-estrogen-receptor-positive-breast-cancer
#20
Pulari U Thangavelu, Cheng-Yu Lin, Srividya Vaidyanathan, Thu H M Nguyen, Eloise Dray, Pascal H G Duijf
During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas...
July 10, 2017: Oncotarget
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