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https://www.readbyqxmd.com/read/29228602/fbxw8-dependent-degradation-of-mrfap1-in-anaphase-controls-mitotic-cell-death
#1
Duan-Zhuo Li, Shun-Fang Liu, Lan Zhu, Yu-Xing Wang, Yi-Xiang Chen, Jie Liu, Gang Hu, Xin Yu, Jian Li, Jin Zhang, Zhi-Xiang Wu, Han Lu, Wei Liu, Bin Liu
Mof4 family associated protein 1 (MRFAP1) is a 14 kDa nuclear protein, which involves in maintaining normal histone modification levels by negatively regulating recruitment of the NuA4 (nucleosome acetyltransferase of H4) histone acetyltransferase complex to chromatin. MRFAP1 has been identified as one of the most up-regulated proteins after NEDD8 (neural precursor cell expressed developmentally down-regulated 8) inhibition in multiple human cell lines. However, the biological function of MRFAP1 and the E3 ligase that targets MRFAP1 for destruction remain mysterious...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222192/suppressor-of-gamma-response-1-links-dna-damage-response-to-organ-regeneration
#2
Ross Alastair Johnson, Phillip Conklin, Michelle Tjahjadi, Victor Missirian, Ted Toal, Siobhan M Brady, Anne B Britt
In Arabidopsis, DNA damage-induced programmed cell death is limited to the meristematic stem cell niche and its early descendants. The significance of this cell-type specific programmed cell death is unclear. Here we demonstrate in roots that it is the programmed destruction of the mitotically-compromised stem cell niche that triggers its regeneration, enabling growth recovery. In contrast to wild-type plants, sog1 plants, which are defective in damage-induced programmed cell death, maintain the cell identities and stereotypical structure of the stem cell niche after irradiation, but these cells fail to undergo cell division, terminating root growth...
December 8, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29209646/re-investigating-plk1-inhibitors-as-antimitotic-agents
#3
Quentin Delacour, Olivier Gavet
Polo-like kinase 1 (PLK1) plays key roles during mitosis, prompting the development of PLK1 inhibitors for anticancer therapy. We recently determined that PLK1 is crucially required for entry into mitosis. Hence, we discuss the potential and limitations of PLK1 inhibition strategies to promote mitotic arrest and death of cancer cells.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29199006/lb-100-a-novel-protein-phosphatase-2a-pp2a-inhibitor-sensitizes-malignant-meningioma-cells-to-the-therapeutic-effects-of-radiation
#4
Winson S C Ho, Saman Sizdahkhani, Shuyu Hao, Hua Song, Ashlee Seldomridge, Anita Tandle, Dragan Maric, Tamalee Kramp, Rongze Lu, John D Heiss, Kevin Camphausen, Mark R Gilbert, Zhengping Zhuang, Deric M Park
Atypical and anaplastic meningiomas (AAM) represent 20% of all meningiomas. They are associated with poor outcomes due to their tendency to recur. While surgery and radiation (RT) are first line therapy, no effective systemic medical treatment has been identified. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in cell cycle regulation and DNA repair. Here, we examined radiosensitizing effects of LB-100, a novel inhibitor of PP2A against AAM as a novel treatment strategy...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29187890/decreased-kpnb1-expression-is-induced-by-plk1-inhibition-and-leads-to-apoptosis-in-lung-adenocarcinoma
#5
Noboru Sekimoto, Yutaka Suzuki, Sumio Sugano
Lung cancer is a major cause of death worldwide, with lung adenocarcinoma being the most frequently diagnosed subtype in Japan. Finding the target of an anticancer drug can improve lung adenocarcinoma treatments. Polo-like kinase 1 (PLK1) is an essential mitotic kinase in mitotic progression, and PLK1 inhibition induces cell cycle arrest and apoptosis in tumor cells. In addition, a variety of PLK1 inhibitors have been identified for cancer treatments. In this study, we looked for the target gene of the anticancer drug that has synergy with PLK1 inhibitors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29170437/the-responses-of-cancer-cells-to-plk1-inhibitors-reveal-a-novel-protective-role-for-p53-in-maintaining-centrosome-separation
#6
Linda Smith, Raed Farzan, Simak Ali, Laki Buluwela, Adrian Saurin, David W Meek
Polo-like kinase-1 (PLK1) plays a major role in driving mitotic events, including centrosome disjunction and separation, and is frequently over-expressed in human cancers. PLK1 inhibition is a promising therapeutic strategy and works by arresting cells in mitosis due to monopolar spindles. The p53 tumour suppressor protein is a short-lived transcription factor that can inhibit the growth, or stimulate the death, of developing cancer cells. Curiously, although p53 normally acts in an anti-cancer capacity, it can offer significant protection against inhibitors of PLK1, but the events underpinning this effect are not known...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157749/mithramycin-a-enhances-tumor-sensitivity-to-mitotic-catastrophe-resulting-from-dna-damage
#7
Bradley T Scroggins, Jeffrey Burkeen, Ayla O White, Eun Joo Chung, Darmood Wei, Su I Chung, Luca F Valle, Shilpa S Patil, Grace McKay-Corkum, Kathryn E Hudak, W Marston Linehan, Deborah E Citrin
PURPOSE: Specificity protein 1 (SP1) is involved in the transcription of several genes implicated in tumor maintenance. We investigated the effects of mithramycin A (MTA), an inhibitor of SP1 DNA binding, on radiation response. METHODS AND MATERIALS: Clonogenic survival after irradiation was assessed in 2 tumor cell lines (A549, UM-UC-3) and 1 human fibroblast line (BJ) after SP1 knockdown or MTA treatment. DNA damage repair was evaluated using γH2AX foci formation, and mitotic catastrophe was assessed using nuclear morphology...
October 12, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29155723/one-step-protocol-for-evaluation-of-the-mode-of-radiation-induced-clonogenic-cell-death-by-fluorescence-microscopy
#8
Daijiro Kobayashi, Atsushi Shibata, Takahiro Oike, Takashi Nakano
Research on ionizing radiation (IR)-induced clonogenic cell death is important for understanding the effect of IR on malignant tumors and normal tissues. Here, we describe a quick and cost-effective one-step assay for simultaneously assessing the major modes of clonogenic cell death induced by IR, i.e., apoptosis, mitotic catastrophe, and cellular senescence. In this method, cells grown on a cover slip are irradiated with X-rays and stained with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI). Using fluorescence microscopy, apoptosis, mitotic catastrophe, and cellular senescence are identified based on the characteristic morphologies of the DAPI-stained nuclei...
October 23, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29150431/the-e3-ubiquitin-ligase-apc-c-c-dh1-degrades-mcph1-after-mcph1-%C3%AE-trcp2-cdc25a-mediated-mitotic-entry-to-ensure-neurogenesis
#9
Xiaoqian Liu, Wen Zong, Tangliang Li, Yujun Wang, Xingzhi Xu, Zhong-Wei Zhou, Zhao-Qi Wang
Mutations of microcephalin (MCPH1) can cause the neurodevelopmental disorder primary microcephaly type 1. We previously showed that MCPH1 deletion in neural stem cells results in early mitotic entry that distracts cell division mode, leading to exhaustion of the progenitor pool. Here, we show that MCPH1 interacts with and promotes the E3 ligase βTrCP2 to degrade Cdc25A independent of DNA damage. Overexpression of βTrCP2 or the knockdown of Cdc25A remedies the high mitotic index and rescues the premature differentiation of Mcph1-deficient neuroprogenitors in vivo MCPH1 itself is degraded by APC/C(C)(dh1), but not APC/C(C)(dc20), in late mitosis and G1 phase...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#10
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29129638/an-attachment-independent-biochemical-timer-of-the-spindle-assembly-checkpoint
#11
Junbin Qian, Maria Adelaida García-Gimeno, Monique Beullens, Maria Giulia Manzione, Gerd Van der Hoeven, Juan Carlos Igual, Miguel Heredia, Pascual Sanz, Lendert Gelens, Mathieu Bollen
The spindle assembly checkpoint (SAC) generates a diffusible protein complex that prevents anaphase until all chromosomes are properly attached to spindle microtubules. A key step in SAC initiation is the recruitment of MAD1 to kinetochores, which is generally thought to be governed by the microtubule-kinetochore (MT-KT) attachment status. However, we demonstrate that the recruitment of MAD1 via BUB1, a conserved kinetochore receptor, is not affected by MT-KT interactions in human cells. Instead, BUB1:MAD1 interaction depends on BUB1 phosphorylation, which is controlled by a biochemical timer that integrates counteracting kinase and phosphatase effects on BUB1 into a pulse-generating incoherent feedforward loop...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29115590/overexpression-of-lamin-b1-induces-mitotic-catastrophe-in-colon-cancer-lovo-cells-and-is-associated-with-worse-clinical-outcomes
#12
Magdalena Izdebska, Maciej Gagat, Alina Grzanka
Lamins are the major components of the nuclear lamina and play important roles in many cellular processes. The role of lamins in cancer development and progression is still unclear but it is known that reduced expression of lamin B1 has been observed in colon cancer. Thus, the aim of the present study was to elucidate the influence of LMNB1 upregulation on colon cancer cell line after treatment with 5-FU. The results indicate, that overexpression of LMNB1 induced dose-dependent cell death mainly by mitotic catastrophe pathway...
November 1, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29109414/involvement-of-autophagy-in-the-outcome-of-mitotic-catastrophe
#13
Irina V Sorokina, Tatiana V Denisenko, Gabriela Imreh, Pyotr A Tyurin-Kuzmin, Vitaliy O Kaminskyy, Vladimir Gogvadze, Boris Zhivotovsky
Evading cell death is a major driving force for tumor progression that is one of the main problems in current cancer research. Mitotic catastrophe (MC) represents attractive platform compromising tumor resistance to current therapeutic modalities. MC appeared as onco-suppressive mechanism and is defined as a stage driving the cell to an irreversible destiny, i.e. cell death via apoptosis or necrosis. Our study highlights that MC induction in colorectal carcinoma cell lines ultimately leads to the autophagy followed by apoptosis...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29104053/polyoma-small-t-upregulates-the-expression-of-cytoskeletal-proteins-in-mammalian-cells-during-mitosis
#14
Irfana Reshi, Zarka Sarwar, Sameer Ahmed Bhat, Syed Qaaifah Gillani, Misbah Shah, Khalid Majid Fazili, Shaida Andrabi
Mammalian cells expressing murine polyoma small T antigen are known to undergo prolonged mitotic arrest followed by extensive cell death. However, the detailed mechanism of this process is not fully understood. While studying the mechanism related to small T induced mitotic arrest in mammalian cells, we observed the expression of various cytoskeletal proteins was unusually altered in polyoma small T expressing cell line. Since most of the cytoskeletal proteins are reoriented during mitosis and are involved in spindle formation, so it was pertinent to investigate the expression of these genes in PyST expressing cell line...
November 2, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29097284/mechanism-of-radioprotection-by-dihydroxy-1-selenolane-dhs-effect-of-fatty-acid-conjugation-and-role-of-glutathione-peroxidase-gpx
#15
Prachi Verma, Amit Kunwar, Kenta Arai, Michio Iwaoka, K Indira Priyadarsini
Dihydroxy-1-selenolane (DHS) previously reported to exhibit radioprotective activity was investigated to understand its mechanism of action in CHO cells of epithelial origin. DHS pre-treatment at 25 μM for 16 h significantly protected CHO cells from radiation (4-11 Gy)-induced delayed mitotic cell death. Further to examine, how increased cellular uptake can influence this mechanism, studies have been performed with DHS-C6, a lipophilic conjugate of DHS. Accordingly CHO cells pre-treated with DHS-C6, showed increased survival against radiation exposure...
October 30, 2017: Biochimie
https://www.readbyqxmd.com/read/29093088/polyploidy-and-mitotic-cell-death-are-two-distinct-hiv-1-vpr-driven-outcomes-in-renal-tubule-epithelial-cells
#16
Emily H Payne, Dhivya Ramalingam, Donald T Fox, Mary E Klotman
Prior studies found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy remained unclear. Here, we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). As in many cell types, we find that Vpr first initiates a G2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29092660/identification-of-dise-inducing-shrnas-by-monitoring-cellular-responses
#17
Monal Patel, Marcus E Peter
Off-target effects (OTE) are an undesired side effect of RNA interference (RNAi) caused by partial complementarity between the targeting siRNA and mRNAs other than the gene to be silenced. The death receptor CD95 and its ligand CD95L contain multiple sequences that when expressed as either si- or shRNAs kill cancer cells through a defined OTE that targets critical survival genes. Death induced by survival gene elimination (DISE) is characterized by specific morphological changes such as elongated cell shapes, senescence-like enlarged cells, appearance of large intracellular vesicles, release of mitochondrial ROS followed by activation of caspase-2, and induction of a necrotic form of mitotic catastrophe...
November 1, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29077092/paxx-and-xlf-interplay-revealed-by-impaired-cns-development-and-immunodeficiency-of-double-ko-mice
#18
Vincent Abramowski, Olivier Etienne, Ramy Elsaid, Junjie Yang, Aurélie Berland, Laetitia Kermasson, Benoit Roch, Stefania Musilli, Jean-Paul Moussu, Karelia Lipson-Ruffert, Patrick Revy, Ana Cumano, François D Boussin, Jean-Pierre de Villartay
The repair of DNA double-stranded breaks (DNAdsb) through non-homologous end joining (NHEJ) is a prerequisite for the proper development of the central nervous system and the adaptive immune system. Yet, mice with Xlf or PAXX loss of function are viable and present with very mild immune phenotypes, although their lymphoid cells are sensitive to ionizing radiation attesting for the role of these factors in NHEJ. In contrast, we show here that mice defective for both Xlf and PAXX are embryonically lethal owing to a massive apoptosis of post-mitotic neurons, a situation reminiscent to XRCC4 or DNA Ligase IV KO conditions...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29064326/ligand-and-structure-based-in-silico-studies-to-identify-kinesin-spindle-protein-ksp-inhibitors-as-potential-anticancer-agents
#19
Chandrasekaran Balakumar, Muthusamy Ramesh, Chuin Lean Tham, Samukelisiwe Pretty Khathi, Frank Kozielski, Cherukupalli Srinivasulu, Girish A Hampannavar, Nisar Sayyad, Mahmoud E Soliman, Rajshekhar Karpoormath
Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule-based motor proteins. KSPis responsible for the establishment of the bipolar mitotic spindle which mediates cell division. Inhibition of KSP expedites the blockade of the normal cell cycle during mitosis throughthe generation of monoastralMTarrays that finally cause apoptotic cell death. As KSP is highly expressed in proliferating/cancer cells, it has gained considerable attention as a potential drug target for cancer chemotherapy...
October 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29058879/critical-overview-of-the-use-of-ru-ii-polypyridyl-complexes-as-photosensitizers-in-one-photon-and-two-photon-photodynamic-therapy
#20
Franz Heinemann, Johannes Karges, Gilles Gasser
Photodynamic Therapy (PDT) is an emerging technique to treat certain types of cancer, bacterial, fungal, and viral infections, and skin diseases. In past years, different research groups developed new ruthenium-containing photosensitizers (PSs) with tuned photophysical and biological properties to better fit the requirements of PDT. In this Account, we report and discuss the latest results in this research area, emphasizing particularly our own research. For example, inspired by the DNA intercalating complex [Ru(bpy)2(dppz)](2+) (bpy = 2,2'-bipyridine; dppz = (dipyrido[3,2-a:2',3'-c]phenazine), a series of ruthenium complexes bearing differently functionalized dppz ligands were synthesized to target DNA...
October 23, 2017: Accounts of Chemical Research
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