keyword
MENU ▼
Read by QxMD icon Read
search

PKcs

keyword
https://www.readbyqxmd.com/read/28706768/dna-pk-and-p38-mapk-a-kinase-collusion-in-alzheimer-s-disease
#1
Jyotshna Kanungo
The pathogenesis of Alzheimer's disease (AD), characterized by prevalent neuronal death and extracellular deposit of amyloid plaques, is poorly understood. DNA lesions downstream of reduced DNA repair ability have been reported in AD brains. Neurons predominantly use a mechanism to repair double-strand DNA breaks (DSB), which is non-homologous end joining (NHEJ). NHEJ requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 and p70 subunits...
2017: Brain Disorders & Therapy
https://www.readbyqxmd.com/read/28702857/protein-kinase-c-and-cardiac-dysfunction-a-review
#2
REVIEW
Raphael M Singh, Emanuel Cummings, Constantinos Pantos, Jaipaul Singh
Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually...
July 12, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28700980/aurora-a-kinase-regulates-non-homologous-end-joining-and-poly-adp-ribose-polymerase-function-in-ovarian-carcinoma-cells
#3
Thuy-Vy Do, Jeff Hirst, Stephen Hyter, Katherine F Roby, Andrew K Godwin
Ovarian cancer is usually diagnosed at late stages when cancer has spread beyond the ovary and patients ultimately succumb to the development of drug-resistant disease. There is an urgent and unmet need to develop therapeutic strategies that effectively treat ovarian cancer and this requires a better understanding of signaling pathways important for ovarian cancer progression. Aurora A kinase (AURKA) plays an important role in ovarian cancer progression by mediating mitosis and chromosomal instability. In the current study, we investigated the role of AURKA in regulating the DNA damage response and DNA repair in ovarian carcinoma cells...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699908/expression-of-protein-kinase-c-gamma-promotes-cell-migration-in-colon-cancer
#4
Catríona M Dowling, Sheri L Hayes, James J Phelan, Mary Clare Cathcart, Stephen P Finn, Brian Mehigan, Paul McCormick, John C Coffey, Jacintha O'Sullivan, Patrick A Kiely
Despite extensive efforts, Protein Kinase Cs (PKCs) have proven to be an intractable target in cancer therapies. Traditionally it was accepted that PKCs act as tumour promoters, however new research suggests that PKCs may play an important role in the suppression of cancer. A challenge in targeting PKCs is the limited data available in patient samples. One of the PKC isozymes, PKC gamma, is thought to be present only in the brain and has been largely neglected in the context of cancer. Analysis of gene expression levels of PKC gamma in patient matched normal and colon cancer tissue samples revealed an up-regulation of the gene in the cancer tissue of 54% of the patients examined...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698766/apple-flavonoids-suppress-carcinogen-induced-dna-damage-in-normal-human-bronchial-epithelial-cells
#5
Vazhappilly Cijo George, H P Vasantha Rupasinghe
SCOPE: Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4) against various carcinogen-induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. METHODS AND RESULTS: AF4-pretreated cells were exposed to nicotine-derived nitrosamine ketones (NNK), NNK acetate (NNK-Ae), methotrexate (MTX), and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28696258/effects-of-dna-end-configuration-on-xrcc4-dna-ligase-iv-and-its-stimulation-of-artemis-activity
#6
Christina A Gerodimos, Howard H Y Chang, Go Watanabe, Michael R Lieber
In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand breaks are repaired. Recognition of each broken DNA end by the DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DNA polymerases, and the XRCC4:DNA ligase IV (X4:LIV) complex in an order influenced by the configuration of the two DNA ends at the break site. The endonuclease Artemis improves joining efficiency by functioning in a complex with DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out endonucleolytic cleavage of 5' and 3' overhangs...
July 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28676397/feedback-autophagy-activation-as-a-key-resistance-factor-of-ku-0060648-in-colorectal-cancer-cells
#7
Mintao Mao, Yumei Liu, Xinhai Gao
The current study evaluated the potential anti-colorectal cancer (CRC) activity by Ku-0060648, a novel DNA-PKcs and PI3K duel inhibitor. In both CRC cell lines (HCT-116 and HT-29) and primary human colon cancer cells, Ku-0060648 exposure at nM concentrations efficiently inhibited cell proliferation. Meanwhile, Ku-0060648 provoked apoptosis in CRC cells. Ku-0060648 was yet ineffective to the normal colon epithelial cells. Ku-0060648 blocked PI3K-AKT-mTOR cascade and in-activated DNA-PKcs in CRC cells. Intriguingly, Ku-0060648 treatment induced feedback autophagy activation in HCT-116 cells...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28673093/di-2-ethylhexyl-phthalate-suppresses-il-12p40-production-by-gm-csf-dependent-macrophages-via-the-ppar%C3%AE-tnfaip3-traf6-axis-after-lipopolysaccharide-stimulation
#8
R Yamaguchi, A Sakamoto, T Yamamoto, S Narahara, H Sugiuchi, A Hisada, T Katoh, Y Yamaguchi
Activation of peroxisome proliferator-activated receptor α (PPARα) by di-(2-ethylhexyl) phthalate (DEHP) has an anti-inflammatory effect. This study investigated the potential combined influence of PPARα, tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), and tumor necrosis factor receptor-associated factor 6 (TRAF6) on interleukin (IL)-12p40 production by macrophages exposed to DEHP and stimulated with lipopolysaccharide (LPS). LPS upregulated IL-12p40 expression by granulocyte-macrophage colony-stimulating factor-dependent macrophages (on day 9 of culture), whereas adding DEHP to cultures significantly attenuated the response of IL-12p40 to LPS stimulation...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28671468/synthesis-and-evaluation-of-dimeric-derivatives-of-diacylglycerol-lactones-as-pkc-ligands
#9
Nami Ohashi, Ryosuke Kobayashi, Wataru Nomura, Takuya Kobayakawa, Agnes Czikora, Brienna Herold, Nancy Lewin, Peter M Blumberg, Hirokazu Tamamura
Protein kinase C (PKC) mediates a central cellular signal transduction pathway involved in disorders such as cancer and Alzheimer's disease. PKC is regulated by binding of the second messenger sn-1,2-diacylglycerol (DAG) to its tandem C1 domains, designated C1a and C1b, leading both to PKC activation and to its translocation to the plasma membrane and to internal organelles. Depending on the isoform, there may be differences in the ligand selectivity of the C1a and C1b domains and there is different spacing between the C1 domains of the classical and novel PKCs...
July 3, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28668119/dna-pkcs-allostery-and-dna-double-strand-break-repair-defining-the-structure-and-setting-the-stage
#10
Dimitri Y Chirgadze, David B Ascher, Tom L Blundell, Bancinyane L Sibanda
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is central to the regulation of the DNA damage response and repair through nonhomologous end joining. The structure has proved challenging due to its large size and multiple HEAT repeats. We have recently reported crystals of selenomethionine-labeled DNA-PKcs complexed with native KU80ct194 (KU80 residues 539-732) diffracting to 4.3Å resolution. The novel use of crystals of selenomethionine-labeled protein expressed in HeLa cells has facilitated the use of single anomalous X-ray scattering of this 4128 amino acid, multiple HEAT-repeat structure...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28654064/detection-and-visualization-of-dna-damage-induced-protein-complexes-in-suspension-cell-cultures-using-the-proximity-ligation-assay
#11
Mahnoush Bahjat, Timon A Bloedjes, Amélie van der Veen, Guus de Wilde, Chiel Maas, Jeroen E J Guikema
The DNA damage response orchestrates the repair of DNA lesions that occur spontaneously, are caused by genotoxic stress, or appear in the context of programmed DNA breaks in lymphocytes. The Ataxia-Telangiectasia Mutated kinase (ATM), ATM- and Rad3-Related kinase (ATR) and the catalytic subunit of DNA-dependent Protein Kinase (DNA-PKcs) are among the first that are activated upon induction of DNA damage, and are central regulators of a network that controls DNA repair, apoptosis and cell survival. As part of a tumor-suppressive pathway, ATM and ATR activate p53 through phosphorylation, thereby regulating the transcriptional activity of p53...
June 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28652322/cryo-em-structure-of-the-dna-pk-holoenzyme
#12
Humayun Sharif, Yang Li, Yuanchen Dong, Liyi Dong, Wei Li Wang, Youdong Mao, Hao Wu
DNA-dependent protein kinase (DNA-PK) is a large protein complex central to the nonhomologous end joining (NHEJ) DNA-repair pathway. It comprises the DNA-PK catalytic subunit (DNA-PKcs) and the heterodimer of DNA-binding proteins Ku70 and Ku80. Here, we report the cryo-electron microscopy (cryo-EM) structures of human DNA-PKcs at 4.4-Å resolution and the DNA-PK holoenzyme at 5.8-Å resolution. The DNA-PKcs structure contains three distinct segments: the N-terminal region with an arm and a bridge, the circular cradle, and the head that includes the kinase domain...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28645898/dna-pk-facilitates-piggybac-transposition-by-promoting-paired-end-complex-formation
#13
Yan Jin, Yaohui Chen, Shimin Zhao, Kun-Liang Guan, Yuan Zhuang, Wenhao Zhou, Xiaohui Wu, Tian Xu
The involvement of host factors is critical to our understanding of underlying mechanisms of transposition and the applications of transposon-based technologies. Modified piggyBac (PB) is one of the most potent transposon systems in mammals. However, varying transposition efficiencies of PB among different cell lines have restricted its application. We discovered that the DNA-PK complex facilitates PB transposition by binding to PB transposase (PBase) and promoting paired-end complex formation. Mass spectrometry analysis and coimmunoprecipitation revealed physical interaction between PBase and the DNA-PK components Ku70, Ku80, and DNA-PKcs Overexpression or knockdown of DNA-PK components enhances or suppresses PB transposition in tissue culture cells, respectively...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28645371/ensemble-and-single-molecule-analysis-of-non-homologous-end-joining-in-frog-egg-extracts
#14
Thomas G W Graham, Johannes C Walter, Joseph J Loparo
Non-homologous end joining (NHEJ) repairs the majority of DNA double-strand breaks in human cells, yet the detailed order of events in this process has remained obscure. Here, we describe how to employ Xenopus laevis egg extract for the study of NHEJ. The egg extract is easy to prepare in large quantities, and it performs efficient end joining that requires the core end joining proteins Ku, DNA-PKcs, XLF, XRCC4, and DNA ligase IV. These factors, along with the rest of the soluble proteome, are present at endogenous concentrations, allowing mechanistic analysis in a system that begins to approximate the complexity of cellular end joining...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28641126/dna-requirements-for-interaction-of-the-c-terminal-region-of-ku80-with-the-dna-dependent-protein-kinase-catalytic-subunit-dna-pkcs
#15
Sarvan Kumar Radhakrishnan, Susan P Lees-Miller
Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation induced DNA double strand breaks (DSBs) in human cells. Critical to NHEJ is the DNA-dependent interaction of the Ku70/80 heterodimer with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the DNA-PK holoenzyme. However, precisely how Ku recruits DNA-PKcs to DSBs ends to enhance its kinase activity has remained enigmatic, with contradictory findings reported in the literature. Here we address the role of the Ku80 C-terminal region (CTR) in the DNA-dependent interaction of Ku70/80 with DNA-PKcs using purified components and defined DNA structures...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28633978/airborne-nitro-pahs-induce-nrf2-are-defense-system-against-oxidative-stress-and-promote-inflammatory-process-by-activating-pi3k-akt-pathway-in-a549-cells
#16
Yu Shang, Qian Zhou, Tiantian Wang, Yuting Jiang, Yufang Zhong, Guangren Qian, Tong Zhu, Xinghua Qiu, Jing An
Ambient particulate matter (PM) is a worldwide health issue of concern. However, limited information is available regarding the toxic contributions of the nitro-derivatives of polycyclic aromatic hydrocarbons (nitro-PAHs). This study intend to examine whether 1-nitropyrene (1-NP) and 3-nitrofluoranthene (3-NF) could activate the nuclear factor-erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) antioxidant defense system, and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway participates in regulating pro-inflammatory responses in A549 cells...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28615293/looping-out-mechanism-for-resolution-of-replicative-stress-at-telomeres
#17
Tianpeng Zhang, Zepeng Zhang, Feng Li, Qian Hu, Haiying Liu, Mengfan Tang, Wenbin Ma, Junjiu Huang, Zhou Songyang, Yikang Rong, Shichuan Zhang, Benjamin Pc Chen, Yong Zhao
Repetitive DNA is prone to replication fork stalling, which can lead to genome instability. Here, we find that replication fork stalling at telomeres leads to the formation of t-circle-tails, a new extrachromosomal structure that consists of circular telomeric DNA with a single-stranded tail. Structurally, the t-circle-tail resembles cyclized leading or lagging replication intermediates that are excised from the genome by topoisomerase II-mediated cleavage. We also show that the DNA damage repair machinery NHEJ is required for the formation of t-circle-tails and for the resolution of stalled replication forks, suggesting that NHEJ, which is normally constitutively suppressed at telomeres, is activated in the context of replication stress...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#18
REVIEW
Tomohiro Morio
DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome...
May 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28539821/stabilization-of-4e-bp1-by-pi3k-kinase-and-its-involvement-in-chk2-phosphorylation-in-the-cellular-response-to-radiation
#19
Zi-Jian Yu, Hui-Hui Luo, Zeng-Fu Shang, Hua Guan, Bei-Bei Xiao, Xiao-Dan Liu, Yu Wang, Bo Huang, Ping-Kun Zhou
Objectives: 4E-BP1 is a family member of eIF4E binding proteins (4E-BPs) which act as the suppressors of cap-dependent translation of RNA via competitively associating with cap-bound eIF4E. RNA translation regulation is an important manner to control the cellular responses to a series of stress conditions such as ionizing radiation (IR)-induced DNA damage response and cell cycle controlling. This study aimed to determine the mechanism of 4E-BP1 stabilization and its potential downstream target(s) in the response to IR...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28498431/prkdc-regulates-chemosensitivity-and-is-a-potential-prognostic-and-predictive-marker-of-response-to-adjuvant-chemotherapy-in-breast-cancer-patients
#20
Gang Sun, Le Yang, Chao Dong, Bin Ma, Meihui Shan, Binlin Ma
DNA-dependent kinase catalytic subunit (DNA-PKcs) is a critical component of DNA repair machinery and is found to be up- or down-regulated in different cancer types. However, its clinical significance in breast cancer remains unclear. To this end, quantitative PCR was performed to measure PRKDC expression level in 59 pairs of breast cancer tissues and the non-tumor adjacent tissues (NATs). The correlation between PRKDC expression and overall survival (OS) as well as the prognostic value of PRKDC were analyzed...
June 2017: Oncology Reports
keyword
keyword
48113
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"