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https://www.readbyqxmd.com/read/29133301/taming-the-beast-control-of-apc-c-cdc20-dependent-destruction
#1
Pablo Lara-Gonzalez, Taekyung Kim, Arshad Desai
The anaphase-promoting complex/cyclosome (APC/C) is a large multisubunit ubiquitin ligase that triggers the metaphase-to-anaphase transition in the cell cycle by targeting the substrates cyclin B and securin for destruction. APC/C activity toward these two key substrates requires the coactivator Cdc20. To ensure that cells enter mitosis and partition their duplicated genome with high accuracy, APC/C(Cdc20) activity must be tightly controlled. Here, we discuss the mechanisms that regulate APC/C(Cdc20) activity both before and during mitosis...
November 13, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29118076/the-meiosis-specific-cdc20-family-member-ama1-promotes-binding-of-the-ssp2-activator-to-the-smk1-map-kinase
#2
Gregory Omerza, Chong Wai Tio, Timothy Philips, Aviva Diamond, Aaron M Neiman, Edward Winter
Smk1 is a meiosis-specific MAP kinase (MAPK) in budding yeast that is required for spore formation. It is localized to prospore membranes (PSMs), the structures that engulf haploid cells during meiosis II (MII). Similar to canonically activated MAPKs, Smk1 is controlled by phosphorylation of its activation-loop threonine (T) and tyrosine (Y). However, activation loop phosphorylation occurs via a non-canonical two-step mechanism in which 1- the cyclin-dependent kinase activating kinase Cak1 phosphorylaytes T207 during MI and 2- Smk1 autophosphorylates Y209 as MII draws to a close...
November 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29115400/global-gene-expression-analysis-combined-with-a-genomics-approach-for-the-identification-of-signal-transduction-networks-involved-in-postnatal-mouse-myocardial-proliferation-and-development
#3
Ruoxin Wang, Chao Su, Xinting Wang, Qiang Fu, Xingjie Gao, Chunyan Zhang, Jie Yang, Xi Yang, Minxin Wei
Mammalian cardiomyocytes may permanently lose their ability to proliferate after birth. Therefore, studying the proliferation and growth arrest of cardiomyocytes during the postnatal period may enhance the current understanding regarding this molecular mechanism. The present study identified the differentially expressed genes in hearts obtained from 24 h‑old mice, which contain proliferative cardiomyocytes; 7‑day‑old mice, in which the cardiomyocytes are undergoing a proliferative burst; and 10‑week‑old mice, which contain growth‑arrested cardiomyocytes, using global gene expression analysis...
November 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29109278/coordinated-regulation-of-heterochromatin-inheritance-by-dpb3-dpb4-complex
#4
Haijin He, Yang Li, Qianhua Dong, An-Yun Chang, Feng Gao, Zhongxuan Chi, Min Su, Faben Zhang, Hyoju Ban, Rob Martienssen, Yu-Hang Chen, Fei Li
During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the inheritance of H3K9 methylation during DNA replication depends on the catalytic subunit of DNA polymerase epsilon, Cdc20. Here we show that the histone-fold subunit of Pol epsilon, Dpb4, interacts an uncharacterized small histone-fold protein, SPCC16C4...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29108461/cdc20-overexpression-is-involved-in-temozolomide-resistant-glioma-cells-with-epithelial-mesenchymal-transition
#5
Jianjiao Wang, Fenggang Zhou, Yang Li, Qingsong Li, Zhichao Wu, Lili Yu, Fei Yuan, Jie Liu, Yu Tian, Yu Cao, Yan Zhao, Yongri Zheng
Glioma remains one of the most aggressive and lethal cancers in central nervous system. Temozolomide (TMZ) is the most commonly used chemotherapeutic agent in gliomas. However, therapeutic benefits of TMZ could be very limited and all patients would finally suffer from tumor progression as the tumors develop resistance to TMZ. In this study, we aim to investigate the underlying mechanism of chemoresistance in glioma cell line and to identify whether there is still a close link between epithelial-mesenchymal transition (EMT) and TMZ resistance in gliomas...
November 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29092815/the-kinase-domain-residue-serine-173-of-s-pombe-chk1-kinase-is-critical-for-the-response-to-dna-replication-stress
#6
Naomi Coulton, Thomas Caspari
While mammalian Chk1 kinase regulates replication origins, safeguards fork integrity and promotes fork progression, yeast Chk1 acts only in G1 and G2. We report here that the mutation of serine 173 (S173A) in the kinase domain of fission yeast Chk1 abolishes the G1-M and S-M checkpoints with little impact on the G2-M arrest. This separation-of-function mutation strongly reduces the Rad3-dependent phosphorylation of Chk1 at serine 345 during logarithmic growth, but not when cells experience exogenous DNA damage...
November 1, 2017: Biology Open
https://www.readbyqxmd.com/read/29084198/distinct-kinetics-of-serine-and-threonine-dephosphorylation-are-essential-for-mitosis
#7
Jamin B Hein, Emil P T Hertz, Dimitriya H Garvanska, Thomas Kruse, Jakob Nilsson
Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains unexplored. Here we demonstrate that the phosphothreonine preference of PP2A-B55 provides an essential regulatory element of mitotic exit. To allow rapid activation of the anaphase-promoting complex/cyclosome (APC/C) co-activator Cdc20, inhibitory phosphorylation sites are conserved as threonines while serine substitutions delay dephosphorylation and Cdc20 activation...
October 30, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29084003/a-genome-wide-comprehensive-analysis-of-alterations-in-driver-genes-in-non-small-cell-lung-cancer
#8
Jun Yi, Xiang Wei, Xinqiang Li, Lei Wan, Jiashou Dong, Rui Wang
Lung cancer is one of the most common malignancies and the leading cause of cancer-related deaths worldwide. Although many oncogenes and tumor suppressors have been uncovered in the past decades, the pathogenesis and mechanisms of lung tumorigenesis and progression are unclear. The advancement of high-throughput sequencing technique and bioinformatics methods has led to the discovery of some unknown important protein-coding genes or noncoding RNAs in human cancers. In this study, we tried to identify and validate lung cancer driver genes to facilitate the diagnosis and individualized treatment of patients with this disease...
October 27, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28980876/cell-division-cycle-20-promotes-cell-proliferation-and-invasion-and-inhibits-apoptosis-in-osteosarcoma-cells
#9
Guanning Shang, Xu Ma, Gang Lv
Cdc20 (cell division cycle 20 homologue) has been reported to exhibit an oncogenic role in human tumorigenesis. However, the function of Cdc20 in osteosarcoma (OS) has not been investigated. In the current study, we aim to explore the role of Cdc20 in human OS cells. Multiple approaches were used to measure cell growth, apoptosis, cell cycle, migration and invasion in OS cells after depletion of Cdc20 or overexpression of Cdc20. We found that down-regulation of Cdc20 inhibited cell growth, induced apoptosis and triggered cell cycle arrest in OS cells...
October 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28951153/susceptibility-of-human-cumulus-cells-to-bisphenol-a-in-vitro
#10
Abdallah Mansur, Michal Adir, Catherine Racowsky, Catherine Mh Combelles, Natalie Landa, Ronit Machtinger
Bisphenol A (BPA) is detectable in follicular fluid. However, the effect of BPA exposure on human cumulus cells (CC) that surround the oocyte and are crucial for oocyte competence has been largely unexplored. We exposed primary cultures of CC to increasing concentrations of BPA [0,0.002, 0.02 and 20μg/mL] and tested the effects of BPA on the expression of genes associated with apoptosis using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR); we also assessed the effect of BPA on apoptosis by staining with anti-caspase 3...
September 22, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28939057/the-cks1-cks2-axis-fine-tunes-mll1-expression-and-is-crucial-for-mll-rearranged-leukaemia-cell-viability
#11
William Grey, Adam Ivey, Thomas A Milne, Torsten Haferlach, David Grimwade, Frank Uhlmann, Edwige Voisset, Veronica Yu
The Cdc28 protein kinase subunits, Cks1 and Cks2, play dual roles in Cdk-substrate specificity and Cdk-independent protein degradation, in concert with the E3 ubiquitin ligase complexes SCF(Skp2) and APC(Cdc20). Notable targets controlled by Cks include p27 and Cyclin A. Here, we demonstrate that Cks1 and Cks2 proteins interact with both the Mll(N) and Mll(C) subunits of Mll1 (Mixed-lineage leukaemia 1), and together, the Cks proteins define Mll1 levels throughout the cell cycle. Overexpression of CKS1B and CKS2 is observed in multiple human cancers, including various MLL-rearranged (MLLr) AML subtypes...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28931595/cell-cycle-transitions-a-common-role-for-stoichiometric-inhibitors
#12
Michael Hopkins, John J Tyson, Béla Novák
The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called "checkpoints") if there have been problems in the replication of the chromosomes or their biorientation on the mitotic spindle. These checkpoints are governed by protein-interaction networks, composed of phase-specific cell-cycle activators and inhibitors...
November 7, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28901457/screening-and-identification-of-key-biomarkers-in-hepatocellular-carcinoma-evidence-from-bioinformatic-analysis
#13
Lin Li, Qingsong Lei, Shujun Zhang, Lingna Kong, Bo Qin
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the molecular mechanisms of HCC are still not well understood. To identify the candidate genes in the carcinogenesis and progression of HCC, microarray datasets GSE19665, GSE33006 and GSE41804 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape...
November 2017: Oncology Reports
https://www.readbyqxmd.com/read/28893350/knockdown-of-gab1-inhibits-cellular-proliferation-migration-and-invasion-in-human-oral-squamous-carcinoma-cells
#14
Luyong Xu, Jie Li, Zheng Kuang, Yan Kuang, Hong Wu
Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is to be responsiblefor aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion and cell growth of OSCC cell lines SCC15 and SCC25. We found Gab1 was over-expressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion...
September 6, 2017: Oncology Research
https://www.readbyqxmd.com/read/28821558/defective-cyclin-b1-induction-in-trastuzumab-emtansine-t-dm1-acquired-resistance-in-her2-positive-breast-cancer
#15
MohammadA Sabbaghi, Gabriel Gil-Gómez, Cristina Guardia, Sonia Servitja, Oriol Arpí, Sara García-Alonso, Silvia Menendez, Montserrat Arumi-Uria, Laia Serrano, Marta Salido, Aura Muntasell, Maria Martínez-García, Sandra Zazo, Cristina Chamizo, Paula González-Alonso, Juan Madoz-Gúrpide, Pilar Eroles, Joaquin Arribas, Ignasi Tusquets, Ana Lluch, Atanasio Pandiella, Federico Rojo, Ana Rovira, Joan Albanell
Purpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2-positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance.Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3, and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28810604/hard-clam-extracts-induce-atypical-apoptosis-in-human-gastric-cancer-cells
#16
Eing-Ju Song, Michael W Y Chan, Jyh-Wei Shin, Che-Chun Chen
Hard clams (HCs) are a nutritionally high-quality and popular seafood, and are established to be a potent antitumor food. The aim of the present study was to determine whether HC extracts induce apoptosis in the human gastric cancer cell line, AGS. In contrast with previously reported methods of extraction, crude extracts of HC were obtained by freezing and thawing and by a method free of hot water or organic solvents. The composition, quality and properties of the HC extracts were demonstrated to be stable since the extracts that were evaluated by capillary electrophoresis and HPLC analysis at different timepoints were similar...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28717250/plk1-phosphorylation-of-cap-h2-triggers-chromosome-condensation-by-condensin-ii-at-the-early-phase-of-mitosis
#17
Yuya Kagami, Masaya Ono, Kiyotsugu Yoshida
Condensin complexes play crucial roles in chromosome condensation that is a fundamental process to establish the "rod-like" shape of chromosome structure in mitosis. Failure of the chromosome assembly causes chromosome segregation errors and subsequent genomic instability. However, a molecular mechanism that controls condensin function for the chromosomal organization has not been fully understood. Here, we show that the abundance of CAP-H2, one of the condensin II subunits, is fluctuated during the cell cycle in accordance with Plk1 kinase activity...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698300/kinetochores-accelerate-or-delay-apc-c-activation-by-directing-cdc20-to-opposing-fates
#18
Taekyung Kim, Pablo Lara-Gonzalez, Bram Prevo, Franz Meitinger, Dhanya K Cheerambathur, Karen Oegema, Arshad Desai
Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28670501/pten-is-a-negative-regulator-of-mitotic-checkpoint-complex-during-the-cell-cycle
#19
Byeong H Choi, Steve Xie, Wei Dai
Nuclear PTEN plays an important role during mitosis. To understand the molecular basis by which PTEN mediates mitotic progression, we examined whether PTEN regulated the formation of mitotic checkpoint complex (MCC). We observed that arsenic trioxide, a mitotic inducer, stimulated nuclear translocation of PTEN in a time-dependent manner. PTEN physically interacted with Cdc20 and Mad2, two important components of MCC. Arsenic treatment diminished the physical association of PTEN with BubR1 and Bub3 but not with Cdc20 and Mad2...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28622611/de-novo-transcriptome-sequencing-and-comparative-analysis-to-discover-genes-involved-in-ovarian-maturity-in-strongylocentrotus-nudus
#20
COMPARATIVE STUDY
Zhiying Jia, Qiai Wang, Kaikai Wu, Zhenlin Wei, Zunchun Zhou, Xiaolin Liu
Strongylocentrotus nudus is an edible sea urchin, mainly harvested in China. Correlation studies indicated that S. nudus with larger diameter have a prolonged marketing time and better palatability owing to their precocious gonads and extended maturation process. However, the molecular mechanism underlying this phenomenon is still unknown. Here, transcriptome sequencing was applied to study the ovaries of adult S. nudus with different shell diameters to explore the possible mechanism. In this study, four independent cDNA libraries were constructed, including two from the big size urchins and two from the small ones using a HiSeq™2500 platform...
September 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
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