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https://www.readbyqxmd.com/read/29930206/cdk1-phosphorylation-of-the-dynein-adapter-nde1-controls-cargo-binding-from-g2-to-anaphase
#1
Caitlin L Wynne, Richard B Vallee
Cytoplasmic dynein is involved in diverse cell cycle-dependent functions regulated by several accessory factors, including Nde1 and Ndel1. Little is known about the role of these proteins in dynein cargo binding, and less is known about their cell cycle--dependent dynein regulation. Using Nde1 RNAi, mutant cDNAs, and a phosphorylation site-specific antibody, we found a specific association of phospho-Nde1 with the late G2-M nuclear envelope and prophase to anaphase kinetochores, comparable to the pattern for the Nde1 interactor CENP-F...
June 21, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29930204/cell-adhesion-is-regulated-by-cdk1-during-the-cell-cycle
#2
Matthew C Jones, Janet A Askari, Jonathan D Humphries, Martin J Humphries
In most tissues, anchorage-dependent growth and cell cycle progression are dependent on cells engaging extracellular matrices (ECMs) via integrin-receptor adhesion complexes. In a highly conserved manner, cells disassemble adhesion complexes, round up, and retract from their surroundings before division, suggestive of a primordial link between the cell cycle machinery and the regulation of cell adhesion to the ECM. In this study, we demonstrate that cyclin-dependent kinase 1 (CDK1) mediates this link. CDK1, in complex with cyclin A2, promotes adhesion complex and actin cytoskeleton organization during interphase and mediates a large increase in adhesion complex area as cells transition from G1 into S...
June 21, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29921474/facile-construction-of-fused-benzimidazole-isoquinolinones-that-induce-cell-cycle-arrest-and-apoptosis-in-colorectal-cancer-cells
#3
Liu-Jun He, Dong-Lin Yang, Shi-Qiang Li, Ya-Jun Zhang, Yan Tang, Jie Lei, Brendan Frett, Hui-Kuan Lin, Hong-Yu Li, Zhong-Zhu Chen, Zhi-Gang Xu
Colorectal cancer (CRC) is one of the most frequent, malignant gastrointestinal tumors, and strategies and effectiveness of current therapy are limited. A series of benzimidazole-isoquinolinone derivatives (BIDs) was synthesized and screened to identify novel scaffolds for CRC. Of the compounds evaluated, 7g exhibited the most promising anti-cancer properties. Employing two CRC cell lines, SW620 and HT29, 7g was found to suppress growth and proliferation of the cell lines at a concentration of ∼20 µM. Treatment followed an increase in G2 /M cell cycle arrest, which was attributed to cyclin B1 and cyclin-dependent kinase 1 (CDK1) signaling deficiencies with simultaneous enhancement in p21 and p53 activity...
June 12, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29914080/phosphoproteomics-of-retinoblastoma-a-pilot-study-identifies-aberrant-kinases
#4
Lakshmi Dhevi Nagarajha Selvan, Ravikanth Danda, Anil K Madugundu, Vinuth N Puttamallesh, Gajanan J Sathe, Uma Maheswari Krishnan, Vikas Khetan, Pukhraj Rishi, Thottethodi Subrahmanya Keshava Prasad, Akhilesh Pandey, Subramanian Krishnakumar, Harsha Gowda, Sailaja V Elchuri
Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer...
June 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29907572/mechanistic-insights-into-avian-reovirus-p17-modulated-suppression-of-cell-cycle-cdk-cyclin-complexes-and-enhancement-of-p53-and-cyclin-h-interaction
#5
Hung-Chuan Chiu, Wei-Ru Huang, Tsai-Ling Liao, Pei-I Chi, Brent L Nielsen, Jyung-Hurng Liu, Hung-Jen Liu
The avian reovirus (ARV) p17 protein is a nucleocytoplasmic shuttling protein. Although we have demonstrated that p17 causes cell growth retardation via activation of p53, the precise mechanisms remains unclear. This is the first report that ARV p17 possesses broad inhibitory effects on cell-cycle CDKs, cyclins, CDK/cyclin complexes, and CDK activating kinase (CAK) activity in various mammalian, avian, and cancer cell lines. Suppression of CDK activity by p17 occurs by direct binding to CDKs, cyclins, and CDK/cyclin complexes, transcriptional downregulation of CDKs, cytoplasmic retention of CDKs and cyclins, and inhibition of CAK activity by promoting p53/cyclin H interaction...
June 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29903985/overexpression-of-cbx3-in-pancreatic-adenocarcinoma-promotes-cell-cycle-transition-associated-tumor-progression
#6
Lian-Yu Chen, Chien-Shan Cheng, Chao Qu, Peng Wang, Hao Chen, Zhi-Qiang Meng, Zhen Chen
BACKGROUND: Previous studies showed that Chromobox protein homolog 3 (CBX3) was overexpressed in several types of human cancers, however its pattern and role in pancreatic adenocarcinoma (PAAD) has not yet been understood. The aim of this study was to identify the expression and function of CBX3 in PAAD. METHODS: Data of transcriptomic and protein expression of CBX3 in PAAD were collected from different databases and analyzed. The in vitro and in vivo role of CBX3 in PAAD was examined...
June 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29901724/cyclin-dependent-kinase-1-activity-coordinates-the-chromatin-associated-state-of-oct4-during-cell-cycle-in-embryonic-stem-cells
#7
Hye Ji Kim, Jihoon Shin, Sangho Lee, Tae Wan Kim, Hyonchol Jang, Min Young Suh, Jae-Hwan Kim, In-Young Hwang, Deog Su Hwang, Eun-Jung Cho, Hong-Duk Youn
Cyclin-dependent kinase 1 (Cdk1) is indispensable for embryonic stem cell (ESC) maintenance and embryo development. Even though some reports have described a connection between Cdk1 and Oct4, there is no evidence that Cdk1 activity is directly linked to the ESC pluripotency transcription program. We recently reported that Aurkb/PP1-mediated Oct4 resetting is important to cell cycle maintenance and pluripotency in mouse ESCs (mESCs). In this study, we show that Cdk1 is an upstream regulator of the Oct4 phosphorylation state during cell cycle progression, and it coordinates the chromatin associated state of Oct4 for pluripotency-related gene expression within the cell cycle...
June 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29901224/pathway-focused-gene-expression-profiles-and-immunohistochemistry-detection-identify-contrasting-association-of-caspase-3-casp3-expression-with-prognosis-in-pediatric-classical-hodgkin-lymphoma
#8
Gabriela Vera-Lozada, Priscilla Segges, Claudio Gustavo Stefanoff, Mário Henrique M Barros, Gerald Niedobitek, Rocio Hassan
The search for clinically relevant molecular markers in classical Hodgkin lymphoma (cHL) is hampered by the histopathological complexity of the disease, resulting from the admixture of a small number of neoplastic Hodgkin and Reed-Sternberg (H-RS) cells with an abundant and heterogeneous microenvironment. In this study, we evaluated gene expression profiles of 11 selected genes previously proposed as a molecular score for adult cHL, aiming to validate its application in the pediatric setting. Assays were performed by RT-qPCR from formalin-fixed paraffin-embedded (FFPE) lymph nodes in 80 patients with cHL...
June 14, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29901201/identification-of-the-potential-oncogenes-in-glioblastoma-based-on-bioinformatic-analysis-and-elucidation-of-the-underlying-mechanisms
#9
Yong Zhang, Qiming Xia, Jun Lin
Glioblastoma (GBM) is a common malignant tumour in the human brain, but its molecular mechanisms have not been systematically evaluated. The aim of this study was to identify potential key oncogenes associated with the progression of GBM and to elucidate their mechanisms. The gene expression profile of GSE50161, selected from the Gene Expression Omnibus database, was analysed to find cancer‑associated genes and gene functions in GBM. In total, 486 differentially expressed genes, including 128 upregulated genes, were identified...
June 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29901190/curcumin-suppresses-cardiac-fibroblasts-activities-by-regulating-the-proliferation-and-cell-cycle-via-the-inhibition-of-the-p38-mapk-erk-signaling-pathway
#10
Guanhua Fang, Shaoqin Chen, Qiuyu Huang, Liangwan Chen, Dongshan Liao
Cardiac fibrosis is a deleterious effect of many cardiovascular diseases. Previous studies have shown that curcumin has exhibited protective effects on cardiovascular diseases. The aim of the present study was to evaluate the effects of curcumin on the activity of human cardiac fibroblasts (CFs) and to elucidate the underlying mechanisms involved. Human CFs were incubated with or without curcumin (20 µmol/l) and transforming growth factor β1 (TGF‑β1; 10 ng/ml), and the expression of α‑smooth muscle actin (α‑SMA), collagen type Iα (COLA)‑1 and COLA3 was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis...
June 1, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29901068/mitotic-kinase-pbk-topk-as-a-therapeutic-target-for-adult-t%C3%A2-cell-leukemia-lymphoma
#11
Chie Ishikawa, Masachika Senba, Naoki Mori
Adult T‑cell leukemia/lymphoma (ATLL) is a disorder involving human T-cell leukemia virus type 1 (HTLV‑1)-infected T‑cells characterized by increased clonal neoplastic proliferation. PDZ-binding kinase (PBK) [also known as T‑lymphokine-activated killer cell-originated protein kinase (TOPK)] is a serine/threonine kinase expressed in proliferative cells and is phosphorylated during mitosis. In this study, the expression and phosphorylation of PBK/TOPK were examined by western blot analysis and RT‑PCR...
June 1, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29899453/a-cdk9-pp1-switch-regulates-the-elongation-termination-transition-of-rna-polymerase-ii
#12
Pabitra K Parua, Gregory T Booth, Miriam Sansó, Bradley Benjamin, Jason C Tanny, John T Lis, Robert P Fisher
The end of the RNA polymerase II (Pol II) transcription cycle is strictly regulated to prevent interference between neighbouring genes and to safeguard transcriptome integrity 1 . The accumulation of Pol II downstream of the cleavage and polyadenylation signal can facilitate the recruitment of factors involved in mRNA 3'-end formation and termination 2 , but how this sequence is initiated remains unclear. In a chemical-genetic screen, human protein phosphatase 1 (PP1) isoforms were identified as substrates of positive transcription elongation factor b (P-TEFb), also known as the cyclin-dependent kinase 9 (Cdk9)-cyclin T1 (CycT1) complex 3 ...
June 13, 2018: Nature
https://www.readbyqxmd.com/read/29896209/schaftoside-interacts-with-nlcdk1-protein-a-mechanism-of-rice-resistance-to-brown-planthopper-nilaparvata-lugens
#13
Pei-Ying Hao, Ya-Lin Feng, Yi-Shen Zhou, Xin-Mi Song, Hong-Liang Li, Yan Ma, Cheng-Long Ye, Xiao-Ping Yu
Brown planthopper (BPH) Nilaparvata lugens Stål is a serious insect pest of rice in Asian countries. Active compounds have close relationship with rice resistance against BPH. In this study, HPLC, MS/MS, and NMR techniques were used to identify active compounds in total flavonoids of rice. As a result, a BPH resistance-associated compound, Peak 1 in HPLC chromatogram of rice flavonoids, was isolated and identified as schaftoside. Feeding experiment with artificial diet indicated that schaftoside played its role in a dose dependent manner, under the concentration of 0...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29895969/inhibition-of-maternal-embryonic-leucine-zipper-kinase-with-otssp167-displays-potent-anti-leukemic-effects-in-chronic-lymphocytic-leukemia
#14
Ya Zhang, Xiangxiang Zhou, Ying Li, Yangyang Xu, Kang Lu, Peipei Li, Xin Wang
TP53 pathway defects contributed to therapy resistance and adverse clinical outcome in chronic lymphocytic leukemia (CLL), which represents an unmet clinical need with few therapeutic options. Maternal embryonic leucine zipper kinase (MELK) is a novel oncogene, which plays crucial roles in mitotic progression and stem cell maintenance. OTSSP167, an orally administrated inhibitor targeting MELK, is currently in a phase I/II clinical trial in patients with advanced breast cancer and acute myeloid leukemia. Yet, no investigation has been elucidated to date regarding the oncogenic role of MELK and effects of OTSSP167 in chronic lymphocytic leukemia (CLL)...
June 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29895527/the-role-of-gsk3-and-its-reversal-with-gsk3-antagonism-in-everolimus-resistance
#15
Elke Tatjana Aristizabal Prada, Gerald Spoettl, Julian Maurer, Michael Lauseker, Eva Koziolek, Jörg Schrader, Ashley B Grossman, Karel Pacak, Felix Beuschlein, Christoph J Auernhammer, Svenja Nölting
Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis. The mTORC1 inhibitor everolimus has been approved for the treatment of advanced NETs. However, the regular development of resistance to everolimus limits its clinical efficacy. We established two independent everolimus-resistant panNET (BON1) cell lines (BON1 RR1, BON1 RR2) to find potential mechanisms of resistance. After 24 weeks of permanent exposure to 10 nM everolimus, BON1 RR1 and BON1 RR2 showed stable resistance with cellular survival rates of 96...
June 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29895190/the-contribution-of-dna-replication-stress-marked-by-high-intensity-pan-nuclear-%C3%AE-h2ax-staining-to-chemosensitization-by-chk1-and-wee1-inhibitors
#16
Leslie A Parsels, Joshua D Parsels, Daria M Tanska, Jonathan Maybaum, Theodore S Lawrence, Meredith A Morgan
Small molecule inhibitors of the checkpoint proteins CHK1 and WEE1 are currently in clinical development in combination with the antimetabolite gemcitabine. It is unclear, however, if there is a therapeutic advantage to CHK1 vs. WEE1 inhibition for chemosensitization. The goals of this study were to directly compare the relative efficacies of the CHK1 inhibitor MK8776 and the WEE1 inhibitor AZD1775 to sensitize pancreatic cancer cell lines to gemcitabine and to identify pharmacodynamic biomarkers predictive of chemosensitization...
June 12, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29893470/cip2a-facilitates-the-g1-s-cell-cycle-transition-via-b-myb-in-human-papillomavirus-16-oncoprotein-e6-expressing-cells
#17
Yonghao Tian, Hanxiang Chen, Lijun Qiao, Wenhao Zhang, Jingyi Zheng, Weiming Zhao, Jason J Chen, Weifang Zhang
Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer...
June 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29891449/-lithium-chloride-arrests-hk-2-cell-cycle-in-g2-phase-through-akt-gsk-3%C3%AE-signal-pathway
#18
Ting-Ting Jiang, Wen-Ying Zhang, Xiao-Hong Xiang, Shuang-Shuang Shu, Wei Xie, Xun Tang, Jun Zhang
OBJECTIVE: To investigate the effect of lithium chloride (LiCl) on cell cycle of HK-2 cells and explore the possible pathways involved. METHODS: HK-2 cells were treated with LiCl at different concentrations (5, 12.5, 20, and 25 mmol/L) for 12, 24, 48, or 72 h, and the changes in cell cycle and viability were detected using flow cytometry and CCK-8 assay, respectively. Western blotting was used to analyze the changes in the expressions of cyclin B1 and CDK1 (the two G2 phase-related proteins) and those of AKT/GSK-3β signaling pathway-related proteins in the treated cells...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29884303/cdk1-inhibition-facilitates-formation-of-syncytiotrophoblasts-and-expression-of-human-chorionic-gonadotropin
#19
Rahim Ullah, Saira Dar, Tanvir Ahmad, Christelle de Renty, Mohammad Usman, Melvin L DePamphilis, Amir Faisal, Syed Shahzad-Ul-Hussan, Zakir Ullah
AIMS: The human placental syncytiotrophoblast (STB) cells play essential roles in embryo implantation and nutrient exchange between the mother and the fetus. STBs are polyploid which are formed by fusion of diploid cytotrophoblast (CTB) cells. Abnormality in STBs formation can result in pregnancy-related disorders. While a number of genes have been associated with CTB fusion the initial events that trigger cell fusion are not well understood. Primary objective of this study was to enhance our understanding about the molecular mechanism of placental cell fusion...
June 2018: Placenta
https://www.readbyqxmd.com/read/29881774/nucleolar-integrity-during-interphase-supports-faithful-cdk1-activation-and-mitotic-entry
#20
Yuki Hayashi, Akiko Fujimura, Kazashi Kato, Rina Udagawa, Toru Hirota, Keiji Kimura
The nucleolus is a dynamic nuclear body that has been demonstrated to disassemble at the onset of mitosis; the relationship between cell cycle progression and nucleolar integrity, however, remains poorly understood. We studied the role of nucleolar proteins in mitosis by performing a global analysis using small interfering RNAs specific to nucleolar proteins; we focused on nucleolar protein 11 (NOL11), with currently unknown mitotic functions. Depletion of NOL11 delayed entry into the mitotic phase owing to increased inhibitory phosphorylation of cyclin-dependent kinase 1 (Cdk1) and aberrant accumulation of Wee1, a kinase that phosphorylates and inhibits Cdk1...
June 2018: Science Advances
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