keyword
MENU ▼
Read by QxMD icon Read
search

Cdk2

keyword
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#1
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539972/site-specific-regulation-of-histone-h1-phosphorylation-in-pluripotent-cell-differentiation
#2
Ruiqi Liao, Craig A Mizzen
BACKGROUND: Structural variation among histone H1 variants confers distinct modes of chromatin binding that are important for differential regulation of chromatin condensation, gene expression and other processes. Changes in the expression and genomic distributions of H1 variants during cell differentiation appear to contribute to phenotypic differences between cell types, but few details are known about the roles of individual H1 variants and the significance of their disparate capacities for phosphorylation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28537766/pirfenidone-induces-g1-arrest-in-human-tenon-s-fibroblasts-in-vitro-involving-akt-and-mapk-signaling-pathways
#3
Xiujuan Guo, Yangfan Yang, Liling Liu, Xiaoan Liu, Jiangang Xu, Kaili Wu, Minbin Yu
PURPOSE: To investigate the underlying mechanism by which pirfenidone blocks the transition from the G1 to S phase in primary human Tenon's fibroblasts. METHODS: Primary human Tenon's fibroblasts were characterized by immunocytofluorescence staining with vimentin, fibroblast surface protein, and cytokeratin. After treating Tenon's fibroblasts with pirfenidone under proliferation conditions (10% fetal bovine serum), cell proliferation was measured using a WST-1 assay...
May 24, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28533114/2-aminomethylthieno-3-2-d-pyrimidin-4-3h-ones-bearing-3-methylpyrazole-hinge-binding-moiety-highly-potent-selective-and-time-dependent-inhibitors-of-cdc7-kinase
#4
Osamu Kurasawa, Misaki Homma, Yuya Oguro, Tohru Miyazaki, Kouji Mori, Noriko Uchiyama, Kenichi Iwai, Akihiro Ohashi, Hideto Hara, Sei Yoshida, Nobuo Cho
In order to increase the success rate for developing new Cdc7 inhibitors for cancer therapy, we explored a new chemotype which can comply with the previously-constructed pharmacophore model. Substitution of a pyridine ring of a serendipitously-identified Cdc7 inhibitor 2b with a 3-methylpyrazole resulted in a 4-fold increase in potency and acceptable kinase selectivity, leading to the identification of thieno[3,2-d]pyrimidin-4(3H)-one as an alternative scaffold. Structure-activity relationship (SAR) study revealed that incorporation of a substituted aminomethyl group into the 2-position improved kinase selectivity...
May 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28521470/new-role-of-human-ribosomal-protein-s3-regulation-of-cell-cycle-via-phosphorylation-by-cyclin-dependent-kinase-2
#5
Se Hee Han, Ji Hyung Chung, Joon Kim, Key-Sun Kim, Ye Sun Han
Human ribosomal protein S3 (hRpS3) is a component of the 40S ribosomal subunit that associated in protein synthesis. hRpS3 has additional ribosomal functions such as DNA repair, transcription, metastasis, and apoptosis via interaction with numerous signaling molecules and has different modifications. Cyclin-dependent kinases (CDKs) are heterodimeric serine/threonine protein kinases that regulate cell cycle progression. Among its members, the Cdk1-cyclin B complex is known to control cell progression in the G2/M phase, while Cdk2-cyclin E/A complexes function in G1/S and S/G2 transition...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520165/targeting-ccl4-induced-liver-fibrosis-by-rna-interference-mediated-inhibition-of-cyclin-e1-in-mice
#6
Jörg-Martin Bangen, Linda Hammerich, Roland Sonntag, Maike Baues, Ute Haas, Daniela Lambertz, Thomas Longerich, Twan Lammers, Frank Tacke, Christian Trautwein, Christian Liedtke
Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSC). Cyclin E1 (CcnE1) is the regulatory subunit of the Cyclin-dependent Kinase 2 (Cdk2) and controls cell cycle re-entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation and survival of HSC and protects from liver fibrogenesis. The aim of the present study was to translate these findings into pre-clinical applications using an RNAi-based approach...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28514656/endogenous-replication-stress-in-mother-cells-leads-to-quiescence-of-daughter-cells
#7
Mansi Arora, Justin Moser, Harsha Phadke, Ashik Akbar Basha, Sabrina L Spencer
Mammalian cells have two fundamentally different states, proliferative and quiescent, but our understanding of how and why cells switch between these states is limited. We previously showed that actively proliferating populations contain a subpopulation that enters quiescence (G0) in an apparently stochastic manner. Using single-cell time-lapse imaging of CDK2 activity and DNA damage, we now show that unresolved endogenous replication stress in the previous (mother) cell cycle prompts p21-dependent entry of daughter cells into quiescence immediately after mitosis...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514208/clinical-significance-and-tumor-suppressive-function-of-mir-516b-in-nonsmall-cell-lung-cancer
#8
Junfei Zhu, Youlin Zhang, Xi Yang, Litong Jin
BACKGROUND: MicroRNA-516b (miR-516b) has been recently reported to be downregulated in nonsmall cell lung cancer (NSCLC). However, its clinical significance and biological function in NSCLC remain to be clarified. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-516b in 82 paired fresh primary tumor tissues and NSCLC cell lines. The association of miR-516b expression with clinicopathological factors and prognosis was statistically analyzed by SPSS 21...
May 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28512636/expression-of-yap-taz-in-keratocystic-odontogenic-tumors-and-its-possible-association-with-proliferative-behavior
#9
Qi-Wen Man, Yan-Qi Ma, Jin-Yuan Liu, Yi Zhao, Bing Liu, Yi-Fang Zhao
The aim of this study is to clarify whether YAP/TAZ is involved in the pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT). The expression levels of YAP/TAZ and downstream proteins and genes in normal oral mucosa (OM) and KCOT were determined and compared by immunohistochemistry and real-time quantitative PCR. The results showed that the expression of YAP/TAZ and downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes (CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are also upregulated in the KCOT...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28508552/real-time-analysis-of-folding-upon-binding-of-a-disordered-protein-by-using-dissolution-dnp%C3%A2-nmr-spectroscopy
#10
Mukundan Ragavan, Luigi I Iconaru, Cheon-Gil Park, Richard W Kriwacki, Christian Hilty
The kinase inhibitory domain of the cell cycle regulatory protein p27(Kip1) (p27) was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D-DNP). While intrinsically disordered in isolation, p27 adopts secondary structural motifs, including an α-helical structure, upon binding to cyclin-dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with hyperpolarization enable the real-time observation of (13) C NMR signals during p27 folding upon binding to Cdk2/cyclin A on a time scale of several seconds...
May 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28504190/expression-and-alternative-splicing-of-the-cyclin-dependent-kinase-inhibitor-3-gene-in-human-cancer
#11
W Douglas Cress, Peng Yu, Jie Wu
The cyclin-dependent kinase inhibitor-3 (CDKN3) gene encodes a dual-specificity protein tyrosine phosphatase that dephosphorylates CDK1/CDK2 and other proteins. CDKN3 is often overexpressed in human cancer, and this overexpression correlates with reduced survival in several types of cancer. CDKN3 transcript variants and mutations have also been reported. The mechanism of CDKN3 overexpression and the role of CDKN3 transcript variants in human cancer are not entirely clear. Here, we review the literature and provide additional data to assess the correlation of CDKN3 expression with patient survival...
May 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28501424/ro0504985-is-an-inhibitor-of-cmgc-kinase-proteins-and-has-anti-human-cytomegalovirus-activity
#12
Blair L Strang
Public-private partnerships allow many previously unavailable compounds to be screened for antiviral activity. Here a screening method was used to identify an oxindole compound, RO0504985, from a Roche kinase inhibitor library that inhibited human cytomegalovirus (HCMV) protein production. RO0504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). However, using kinase selectivity assays it was found that RO0504985 was an inhibitor of several CMGC group kinase proteins, including CDK2...
May 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28498797/natb-mediated-protein-n-%C3%AE-terminal-acetylation-is-a-potential-therapeutic-target-in-hepatocellular-carcinoma
#13
Leire Neri, Marta Lasa, Alberto Elosegui-Artola, Delia D'Avola, Beatriz Carte, Cristina Gazquez, Sara Alve, Pere Roca-Cusachs, Mercedes Iñarrairaegui, Jose Herrero, J Prieto, Bruno Sangro, Rafael Aldabe
The identification of new targets for systemic therapy of hepatocellular carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB catalyzes the N-α-terminal acetylation of 15% of the human proteome and that this action is necessary for proper actin cytoskeleton structure and function. In tumors, cytoskeletal changes influence motility, invasion, survival, cell growth and tumor progression, making the cytoskeleton a very attractive antitumor target. Here, we show that hNatB subunits are upregulated in in over 59% HCC tumors compared to non-tumor tissue and that this upregulation is associated with microscopic vascular invasion...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498480/miconazole-induces-apoptosis-via-the-death-receptor-5-dependent-and-mitochondrial-mediated-pathways-in-human-bladder-cancer-cells
#14
Sheau-Yun Yuan, Ming-Yuh Shiau, Yen-Chuan Ou, Yu-Chia Huang, Cheng-Che Chen, Chen-Li Cheng, Kun-Yuan Chiu, Shian-Shiang Wang, Kan-Jen Tsai
Miconazole (MIC), an antifungal agent, diplays anti‑tumorigenic activity in various types of human cancers, including bladder cancer, yet its mechanism of antitumor action is not well understood. In the present study, we demonstrated that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and TSGH-8301 bladder cancer cells in a dose- and time‑dependent manner, but did not exhibit significant toxicity toward human peripheral blood mononuclear cells. Cell cycle analysis revealed that MIC at concentrations of 25 and 50 µM significantly caused G0/G1 arrest in the TSGH-8301 and T24 cells, respectively...
April 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498460/mcm7-amplification-and-overexpression-promote-cell-proliferation-colony-formation-and-migration-in-esophageal-squamous-cell-carcinoma-by-activating-the-akt1-mtor-signaling-pathway
#15
Yun-Tan Qiu, Wen-Jun Wang, Bing Zhang, Li-Li Mei, Zhi-Zhou Shi
The roles and mechanisms of mini-chromosome maintenance complex component 7 (MCM7) amplification and overexpression in esophageal carcinogenesis were investigated. By analyzing the TCGA datasets, we found that MCM7 was amplified in approximately 12% of esophageal squamous cell carcinomas (ESCCs), and in more than 4% of head and neck squamous cell carcinomas and stomach carcinomas. Overexpression of MCM7 was further verified in three independent GEO datasets of esophageal cancer. Knockdown of MCM7 using two siRNAs significantly inhibited cell proliferation, colony formation and migration of KYSE510 and EC9706 cells in vitro...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28492347/the-soy-derived-peptide-vglycin-inhibits-the-growth-of-colon-cancer-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#16
Chang Gao, Rui Sun, Ya-Rong Xie, An-Li Jiang, Mei Lin, Min Li, Zheng-Wang Chen, Ping Zhang, Honglin Jin, Jue-Ping Feng
Vglycin, a novel natural polypeptide isolated from pea seeds, possesses antidiabetic properties. Our previous studies have shown that Vglycin can induce the differentiation of human colon adenocarcinoma cells. We aimed to determine the anticancer activity of Vglycin against colon cancer cells and to elucidate related apoptosis-inducing mechanisms. Treatment with purified Vglycin significantly reduced growth, viability, and colony formation of CT-26, SW480, and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating the expression of proliferating cell nuclear antigen...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28486226/role-of-albumin-in-growth-inhibition-in-hepatocellular-carcinoma
#17
Ezgi Bağırsakçı, Eren Şahin, Neşe Atabey, Esra Erdal, Vito Guerra, Brian I Carr
OBJECTIVE: Levels of serum albumin have recently emerged, together with C-reactive protein, as an important prognostic indicator for hepatocellular carcinoma (HCC). It has recently been reported that larger HCCs are associated with lower albumin levels. However, the albumin-mediated growth decrease has yet to be determined. METHODS: We examined a large HCC cohort and then by direct exposure of HCC cells in vitro, the relationship of albumin levels to HCC growth...
May 10, 2017: Oncology
https://www.readbyqxmd.com/read/28482660/accurate-prediction-of-complex-structure-and-affinity-for-a-flexible-protein-receptor-and-its-inhibitor
#18
Gert-Jan Bekker, Narutoshi Kamiya, Mitsugu Araki, Ikuo Fukuda, Yasushi Okuno, Haruki Nakamura
In order to predict the accurate binding configuration as well as the binding affinity for a flexible protein receptor and its inhibitor drug, enhanced sampling with multicanonical molecular dynamics (McMD) simulation and thermodynamic integration (TI) were combined as a general drug docking method. CDK2, cyclin-dependent kinase 2, is involved in the cell cycle regulation. Malfunctions in CDK2 can cause tumorigenesis, and thus it is a potential drug target. Here, we performed a long McMD simulation for docking the inhibitor CS3 to CDK2 starting from the unbound structure...
May 18, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28475144/undariopsis-peterseniana-promotes-hair-growth-by-the-activation-of-wnt-%C3%AE-catenin-and-erk-pathways
#19
Jung-Il Kang, Min-Kyoung Kim, Ji-Hyeok Lee, You-Jin Jeon, Eun-Kyoung Hwang, Young-Sang Koh, Jin-Won Hyun, Soon-Young Kwon, Eun-Sook Yoo, Hee-Kyoung Kang
In this study, we investigated the effect and mechanism of Undariopsis peterseniana, an edible brown alga, on hair growth. The treatment of vibrissa follicles with U. peterseniana extract ex vivo for 21 days significantly increased the hair-fiber lengths. The U. peterseniana extract also significantly accelerated anagen initiation in vivo. Moreover, we found that U. peterseniana extract was able to open the KATP channel, which may contribute to increased hair growth. The U. peterseniana extract decreased 5α-reductase activity and markedly increased the proliferation of dermal papilla cells, a central regulator of the hair cycle...
May 5, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28467776/histoneh3-demethylase-jmjd2a-promotes-growth-of-liver-cancer-cells-through-up-regulating-mir372
#20
Jiahui An, Jie Xu, Jiao Li, Song Jia, Xiaonan Li, Yanan Lu, Yuxin Yang, Zhuojia Lin, Xiaoru Xin, Mengying Wu, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Dongdong Lu
Changes in histone lysine methylation status have been observed during cancer formation. JMJD2A protein is a demethylase that is overexpressed in several tumors. Herein, our results demonstrate that JMJD2A accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, JMJD2A promoted the expression and mature of pre-miR372 epigenetically. Notably, miR372 blocks the editing of 13th exon-introns-14th exon and forms a novel transcript( JMJD2AΔ) of JMJD2A. In particular, JMJD2A inhibited P21(WAF1/Cip1) expression by decreasing H3K9me3 dependent on JMJD2AΔ...
April 13, 2017: Oncotarget
keyword
keyword
57351
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"