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Kan Xing Wu, Patchara Phuektes, Pankaj Kumar, Germaine Yen Lin Goh, Dimitri Moreau, Vincent Tak Kwong Chow, Frederic Bard, Justin Jang Hann Chu
Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation...
October 17, 2016: Nature Communications
Jihoon Shin, Hong-Duk Youn
In embryonic stem cells (ESCs), cell cycle regulation is deeply connected to pluripotency. Especially, core transcription factors (CTFs) which are essential to maintain the pluripotency transcription programs should be reset during M/G1 transition. However, it remains unknown about how CTFs are governed during cell cycle progression. Here, we describe that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) axis during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle related target genes in determining the identity of ESCs...
September 29, 2016: BMB Reports
Si-Jia He, Li-Ping Shu, Zhi-Wei Zhou, Tianxin Yang, Wei Duan, Xueji Zhang, Zhi-Xu He, Shu-Feng Zhou
Leukemia is a common malignancy of blood cells with poor prognosis in many patients. Aurora kinases, a family of serine/threonine kinases, play a key role in regulating cell division and mitosis and are linked to tumorigenesis, metastasis, and poor prognosis in many human cancers including leukemia and lymphoma. Danusertib (Danu) is a pan-inhibitor of Aurora kinases with few data available in leukemia therapy. This study aimed to identify new molecular targets for Aurora kinase inhibition in human leukemia cells using quantitative proteomic analysis followed by verification experiments...
September 6, 2016: Cancer Letters
Xiang Jin, Xingang Liu, Xiaodan Li, Yinghui Guan
Introduction. Lung adenocarcinoma (LAC) is the most frequent type of lung cancer and has a high metastatic rate at an early stage. This study is aimed at identifying LAC-associated genes. Materials and Methods. GSE62950 downloaded from Gene Expression Omnibus included a DNA methylation dataset and an mRNA expression profiles dataset, both of which included 28 LAC tissue samples and 28 adjacent normal tissue samples. The differentially expressed genes (DEGs) were screened by Limma package in R, and their functions were predicted by enrichment analysis using TargetMine online tool...
2016: BioMed Research International
Ana Paula Nunes Rodrigues Alves, João Agostinho Machado-Neto, Priscila Santos Scheucher, Helder Henrique Paiva, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabiola Traina
Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell characterized by presence of the oncoprotein BCR-ABL1, which have constitutive tyrosine kinase activity. BCR-ABL1 activation induces aurora kinase A (AURKA) and aurora kinase B (AURKB) expression, which are serine-threonine kinases that play an important function in chromosome alignment, segregation and cytokinesis during mitosis. Acquisition of resistance to tyrosine kinase inhibitors has emerged as a problem for CML patients and the identification of novel targets with an important contribution for CML phenotype is of interest...
September 2016: Leukemia Research
Maria Maddalena Di Fiore, Alessandra Santillo, Sara Falvo, Salvatore Longobardi, Gabriella Chieffi Baccari
A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade...
2016: International Journal of Molecular Sciences
Jean Christopher Chamcheu, Vaqar Mustafa Adhami, Stephane Esnault, Mario Sechi, Imtiaz A Siddiqui, Kenneth A Satyshur, Deeba N Syed, Shah-Jahan M Dodwad, Maria Ines Chaves-Rodriquez, B Jack Longley, Gary S Wood, Hasan Mukhtar
AIM: The treatment of psoriasis remains elusive, underscoring the need for identifying novel disease targets and mechanism-based therapeutic approaches. We recently reported that the PI3K/Akt/mTOR pathway that is frequently deregulated in many malignancies is also clinically relevant for psoriasis. We also provided rationale for developing delphinidin (Del), a dietary antioxidant for the management of psoriasis. This study utilized high throughput biophysical and biochemical approaches and in-vitro and in-vivo models to identify molecular targets regulated by Del in psoriasis...
July 8, 2016: Antioxidants & Redox Signaling
Meghan Ruebel, Kartik Shankar, Dana Gaddy, Forrest Lindsey, Thomas Badger, Aline Andres
Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n = 7) compared with lean (LN; n = 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P < 0...
July 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Aner Mesic, Marija Rogar, Petra Hudler, Robert Juvan, Radovan Komel
Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes can contribute to susceptibility of human cancer, including gastric cancer (GC). We aimed to investigate the effects of Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC) gene polymorphisms on GC risk in Slovenian population. We genotyped four SNPs in AURKA (rs2273535 and rs1047972), AURKB (rs2241909), and AURKC (rs758099) in a total of 128 GC patients and 372 healthy controls using TaqMan allelic discrimination assays to evaluate their effects on GC risk...
August 2016: IUBMB Life
L Terzaghi, I Tessaro, F Raucci, V Merico, G Mazzini, S Garagna, M Zuccotti, F Franciosi, V Lodde
Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in both oocyte and ovarian somatic cells, where it is found in multiple cellular sub-compartments including the mitotic spindle apparatus. PGRMC1 localization in the maturing bovine oocytes mirrors its localization in mitotic cells, suggesting a possible common action in mitosis and meiosis. To test the hypothesis that altering PGRMC1 activity leads to similar defects in mitosis and meiosis, PGRMC1 function was perturbed in cultured bovine granulosa cells (bGC) and maturing oocytes and the effect on mitotic and meiotic progression assessed...
August 2, 2016: Cell Cycle
Ballachanda N Devaiah, Chanelle Case-Borden, Anne Gegonne, Chih Hao Hsu, Qingrong Chen, Daoud Meerzaman, Anup Dey, Keiko Ozato, Dinah S Singer
Bromodomain protein 4 (BRD4) is a chromatin-binding protein implicated in cancer and autoimmune diseases that functions as a scaffold for transcription factors at promoters and super-enhancers. Although chromatin decompaction and transcriptional activation of target genes are associated with BRD4 binding, the mechanisms involved are unknown. We report that BRD4 is a histone acetyltransferase (HAT) that acetylates histones H3 and H4 with a pattern distinct from those of other HATs. Both mouse and human BRD4 have intrinsic HAT activity...
June 2016: Nature Structural & Molecular Biology
Adrienne Weeks, Sameer Agnihotri, Jennifer Lymer, Alan Chalil, Roberto Diaz, Semra Isik, Christian Smith, James T Rutka
Stress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins epithelial cell transforming 2 and Aurora kinase B (AurkB) are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed using high-throughput fluorescent-based cellomics assays...
June 2016: American Journal of Pathology
An Tang, Peiliang Shi, Anying Song, Dayuan Zou, Yue Zhou, Pengyu Gu, Zan Huang, Qinghua Wang, Zhaoyu Lin, Xiang Gao
Studies using in vitro cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an in vivo model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1(st) meiotic division due to chromosome misalignment and abnormal spindle assembly...
June 2, 2016: Cell Cycle
Cameron T Durlacher, Zhi-Ling Li, Xiao-Wu Chen, Zhi-Xu He, Shu-Feng Zhou
Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation...
June 2016: Clinical and Experimental Pharmacology & Physiology
Alberto Ocaña, Javier Pérez-Peña, Ana Alcaraz-Sanabria, Verónica Sánchez-Corrales, Cristina Nieto-Jiménez, Arnoud J Templeton, Bostjan Seruga, Atanasio Pandiella, Eitan Amir
INTRODUCTION: Accurate assessment of prognosis in early stage ovarian cancer is challenging resulting in suboptimal selection of patients for adjuvant therapy. The identification of predictive markers for cytotoxic chemotherapy is therefore highly desirable. Protein kinases are important components in oncogenic transformation and those relating to cell cycle and mitosis control may allow for identification of high-risk early stage ovarian tumors. METHODS: Genes with differential expression in ovarian surface epithelia (OSE) and ovarian cancer epithelial cells (CEPIs) were identified from public datasets and analyzed with dChip software...
April 19, 2016: Oncotarget
Melissa Schmidt, Andreas Mock, Christine Jungk, Felix Sahm, Anna Theresa Ull, Rolf Warta, Katrin Lamszus, Konstantinos Gousias, Ralf Ketter, Saskia Roesch, Carmen Rapp, Sebastian Schefzyk, Steffi Urbschat, Bernd Lahrmann, Almuth F Kessler, Mario Löhr, Christian Senft, Niels Grabe, David Reuss, Philipp Beckhove, Manfred Westphal, Andreas von Deimling, Andreas Unterberg, Matthias Simon, Christel Herold-Mende
Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade...
March 22, 2016: Oncotarget
Jihoon Shin, Tae Wan Kim, Hyunsoo Kim, Hye Ji Kim, Min Young Suh, Sangho Lee, Han-Teo Lee, Sojung Kwak, Sang-Eun Lee, Jong-Hyuk Lee, Hyonchol Jang, Eun-Jung Cho, Hong-Duk Youn
Pluripotency transcription programs by core transcription factors (CTFs) might be reset during M/G1 transition to maintain the pluripotency of embryonic stem cells (ESCs). However, little is known about how CTFs are governed during cell cycle progression. Here, we demonstrate that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle genes in determining the identity of ESCs. Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle...
2016: ELife
Edmilson Ozorio Dos Santos, Tatiana Correa Carneiro-Lobo, Mateus Nobrega Aoki, Elena Levantini, Daniela Sanchez Bassères
BACKGROUND: Activating mutations in KRAS are prevalent in lung cancer and have been causally linked to the oncogenic process. However, therapies targeted to oncogenic RAS have been ineffective to date and identification of KRAS targets that impinge on the oncogenic phenotype is warranted. Based on published studies showing that mitotic kinases Aurora A (AURKA) and B (AURKB) cooperate with oncogenic RAS to promote malignant transformation and that AURKA phosphorylates RAS effector pathway components, the aim of this study was to investigate whether AURKA and AURKB are KRAS targets in lung cancer and whether targeting these kinases might be therapeutically beneficial...
2016: Molecular Cancer
Sriganesh Srihari, Murugan Kalimutho, Samir Lal, Jitin Singla, Dhaval Patel, Peter T Simpson, Kum Kum Khanna, Mark A Ragan
UNLABELLED: Copy number alterations (CNAs) are thought to account for 85% of the variation in gene expression observed among breast tumours. The expression of cis-associated genes is impacted by CNAs occurring at proximal loci of these genes, whereas the expression of trans-associated genes is impacted by CNAs occurring at distal loci. While a majority of these CNA-driven genes responsible for breast tumourigenesis are cis-associated, trans-associated genes are thought to further abet the development of cancer and influence disease outcomes in patients...
March 2016: Molecular BioSystems
Katalin Hegyi
The main goal of this work was to study the effect of Aurora kinase expression on cell ploidy and tumorigenesis. Fifty invasive breast cancer, 50 diffuse large B-cell lymphoma and 10 reactive lymph node samples were recruited in the study. Because of the significant correlation with the overall cell proliferation rate, the overexpression of Aurora B could not be stated on the basis of kinase expressing tumor cell fractions alone. The relative expression of Aurora B kinase is better reflected by the AMI index which represents the Aurora B expression in relation to the whole proliferative fraction of the tumor...
December 2015: Magyar Onkologia
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