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Leucine zipper kinase

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https://www.readbyqxmd.com/read/28230786/sex-specificity-of-mineralocorticoid-target-gene-expression-during-renal-development-and-long-term-consequences
#1
Laurence Dumeige, Caroline Storey, Lyvianne Decourtye, Melanie Nehlich, Christophe Lhadj, Say Viengchareun, Laurent Kappeler, Marc Lombès, Laetitia Martinerie
Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28222251/prognostic-methylation-markers-for-overall-survival-in-cytogenetically-normal-patients-with-acute-myeloid-leukemia-treated-on-swog-trials
#2
Xiaoyu Qu, Megan Othus, Jerry Davison, Yu Wu, Liying Yan, Soheil Meshinchi, Fabiana Ostronoff, Elihu H Estey, Jerry P Radich, Harry P Erba, Frederick R Appelbaum, Min Fang
BACKGROUND: Aberrant DNA methylation is known to occur in patients with acute myeloid leukemia (AML), whereas methylation signatures and prognostic markers have been proposed. The objective of the current study was to evaluate all CpG sites of the genome and identify prognostic methylation markers for overall survival in patients with AML with normal karyotype (AML-NK). METHODS: AML-NK samples from 7 SWOG trials were analyzed using a novel genome-wide approach called "CHARMcox" (comprehensive high-throughput array-based relative methylation analysis combined with the Cox proportional hazards model) controlling for known clinical covariates...
February 21, 2017: Cancer
https://www.readbyqxmd.com/read/28214016/melk-expression-in-ovarian-cancer-correlates-with-poor-outcome-and-its-inhibition-by-otssp167-abrogates-proliferation-and-viability-of-ovarian-cancer-cells
#3
Reto S Kohler, Henriette Kettelhack, Alexandra M Knipprath-Mészaros, André Fedier, Andreas Schoetzau, Francis Jacob, Viola Heinzelmann-Schwarz
OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis)...
February 14, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28186750/-addition-and-subtraction-selectivity-design-for-type-ii-maternal-embryonic-leucine-zipper-kinase-inhibitors
#4
Xin Chen, John Giraldes, Elizabeth R Sprague, Subarna Shakya, Zhuoliang Chen, Yaping Wang, Carol Joud, Simon Mathieu, Christine Hiu-Tung Chen, Christopher Straub, Jose S Duca, Kristen Hurov, Yanqiu Yuan, Wenlin Shao, B Barry Touré
While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improving the kinase selectivity of type-II maternal embryonic leucine zipper kinase inhibitors by applying these two complementary approaches together, which clearly demonstrates the powerful synergy between them...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28111074/apoe2-apoe3-and-apoe4-differentially-stimulate-app-transcription-and-a%C3%AE-secretion
#5
Yu-Wen Alvin Huang, Bo Zhou, Marius Wernig, Thomas C Südhof
Human apolipoprotein E (ApoE) apolipoprotein is primarily expressed in three isoforms (ApoE2, ApoE3, and ApoE4) that differ only by two residues. ApoE4 constitutes the most important genetic risk factor for Alzheimer's disease (AD), ApoE3 is neutral, and ApoE2 is protective. How ApoE isoforms influence AD pathogenesis, however, remains unclear. Using ES-cell-derived human neurons, we show that ApoE secreted by glia stimulates neuronal Aβ production with an ApoE4 > ApoE3 > ApoE2 potency rank order. We demonstrate that ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28030830/ikaros-regulation-of-the-bcl6-bach2-axis-and-its-clinical-relevance-in-acute-lymphoblastic-leukemia
#6
Zheng Ge, Xilian Zhou, Yan Gu, Qi Han, Jianyong Li, Baoan Chen, Qinyu Ge, Elanora Dovat, Jonathon L Payne, Tianyu Sun, Chunhua Song, Sinisa Dovat
B-Cell CLL/Lymphoma 6 (BCL6) is a proto-oncogene that is highly expressed in acute lymphoblastic leukemia (ALL). BTB and CNC Homology 1 Basic Leucine Zipper Transcription Factor 2 (BACH2) is a suppressor of transcription. The BACH2-BCL6 balance controls selection at the pre-B cell receptor checkpoint by regulating p53 expression. However, the underlying mechanism and the clinical relevance of the BCL6/BACH2 axis are unknown. Here, we found that Ikaros, a tumor suppressor encoded by IKZF1, directly binds to both the BCL6 and BACH2 promoters where it suppresses BCL6 and promotes BACH2 expression in B-cell ALL (B-ALL) cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28018412/the-role-and-regulation-of-abi5-aba-insensitive-5-in-plant-development-abiotic-stress-responses-and-phytohormone-crosstalk
#7
REVIEW
Anna Skubacz, Agata Daszkowska-Golec, Iwona Szarejko
ABA Insensitive 5 (ABI5) is a basic leucine zipper transcription factor that plays a key role in the regulation of seed germination and early seedling growth in the presence of ABA and abiotic stresses. ABI5 functions in the core ABA signaling, which is composed of PYR/PYL/RCAR receptors, PP2C phosphatases and SnRK2 kinases, through the regulation of the expression of genes that contain the ABSCISIC ACID RESPONSE ELEMENT (ABRE) motif within their promoter region. The regulated targets include stress adaptation genes, e...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28017720/retinal-expression-and-localization-of-mef2c-support-its-important-role-in-photoreceptor-gene-expression
#8
Anne Wolf, Alexander Aslanidis, Thomas Langmann
Photoreceptor-specific gene expression is controlled by a hierarchical network of transcription factors, including the master regulators cone-rod homeobox (Crx) and neural retina leucine zipper (Nrl). Myocyte-enhancer factor 2c (Mef2c) is an ubiquitously expressed transcription factor with important functions in the cardiovascular system. Here, we performed a detailed analysis of Mef2c expression, localization and function in the retina to further elucidate its potential role for photoreceptor gene regulation...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28009276/mitochondria-localize-to-injured-axons-to-support-regeneration
#9
Sung Min Han, Huma S Baig, Marc Hammarlund
Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo, single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons so that average mitochondria density increases after injury. Moreover, single-neuron analysis reveals that axons that fail to increase mitochondria have poor regeneration...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27920471/identification-of-il11ra-and-melk-amplification-in-gastric-cancer-by-comprehensive-genomic-profiling-of-gastric-cancer-cell-lines
#10
Danielle Queiroz Calcagno, Sylvia Santomi Takeno, Carolina Oliveira Gigek, Mariana Ferreira Leal, Fernanda Wisnieski, Elizabeth Suchi Chen, Taíssa Maíra Thomaz Araújo, Eleonidas Moura Lima, Maria Isabel Melaragno, Samia Demachki, Paulo Pimentel Assumpção, Rommel Rodriguez Burbano, Marília Cardoso Smith
AIM: To identify common copy number alterations on gastric cancer cell lines. METHODS: Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS: The amplification of 9p13...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27915972/resistance-to-cell-death-and-its-modulation-in-cancer-stem-cells
#11
Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27899501/unraveling-fungal-radiation-resistance-regulatory-networks-through-the-genome-wide-transcriptome-and-genetic-analyses-of-cryptococcus-neoformans
#12
Kwang-Woo Jung, Dong-Hoon Yang, Min-Kyu Kim, Ho Seong Seo, Sangyong Lim, Yong-Sun Bahn
The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27859413/zak%C3%AE-antagonizes-and-ameliorates-the-cardiac-hypertrophic-and-apoptotic-effects-induced-by-zak%C3%AE
#13
Chien-Yao Fu, Wei-Wen Kuo, Tsung-Jung Ho, Su-Ying Wen, Ling-Chun Lin, Yan-Shen Tseng, Hui-Chuan Hung, Vijaya Padma Viswanadha, Jaw-Ji Yang, Chih-Yang Huang
ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS-dependent pathway and a mitochondria-dependent pathway by subsequently inducing caspase-3...
December 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27798878/expression-of-maternal-embryonic-leucine-zipper-kinase-melk-correlates-to-malignant-potentials-in-hepatocellular-carcinoma
#14
Kiyokazu Hiwatashi, Shinichi Ueno, Masahiko Sakoda, Satoshi Iino, Koji Minami, Keiichi Yonemori, Yuka Nishizono, Hiroshi Kurahara, Yuko Mataki, Kosei Maemura, Hiroyuki Shinchi, Shoji Natsugoe
BACKGROUND/AIM: Maternal embryonic leucine zipper kinase (MELK) is categorized as a member of AMP-activated protein kinase families. Various MELK-associated cellular and biological processes affect multiple stages of tumorigenesis. The aim of the present study was to clarify the relationship between MELK expression and hepatocellular carcinoma (HCC) clinicopathological features. MATERIALS AND METHODS: In thirty conserved frozen primary HCC and non-HCC samples MELK mRNA expression was examined by quantitative real-time polymerase chain reaction (PCR)...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27783979/a-requirement-for-zak-kinase-activity-in-canonical-tgf-%C3%AE-signaling
#15
Shyam Nyati, Areeb Chator, Katerina Schinske, Brandon S Gregg, Brian Dale Ross, Alnawaz Rehemtulla
The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7), is a MAPK-kinase kinase (MKKK). Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK) pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β)-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27754177/sy-15-4-role-of-histone-deacetylases-in-regulating-endothelial-and-vascular-function
#16
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27725371/mypt1-isoforms-expressed-in-hek293t-cells-are-differentially-phosphorylated-after-gtp%C3%AE-s-treatment
#17
Simon Lin, Frank V Brozovich
Agonist stimulation of smooth muscle is known to activate RhoA/Rho kinase signaling, and Rho kinase phosphorylates the myosin targeting subunit (MYPT1) of myosin light chain (MLC) phosphatase at Thr696 and Thr853, which inhibits the activity of MLC phosphatase to produce a Ca(2+) independent increase in MLC phosphorylation and force (Ca(2+) sensitization). Alternative mRNA splicing produces four MYPT1 isoforms, which differ by the presence or absence of a central insert (CI) and leucine zipper (LZ). This study was designed to determine if Rho kinase differentially phosphorylates MYPT1 isoforms...
2016: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
https://www.readbyqxmd.com/read/27693640/melk-is-an-oncogenic-kinase-essential-for-early-hepatocellular-carcinoma-recurrence
#18
Hongping Xia, Shik Nie Kong, Jianxiang Chen, Ming Shi, Karthik Sekar, Veerabrahma Pratap Seshachalam, Muthukumar Rajasekaran, Brian Kim Poh Goh, London Lucien Ooi, Kam M Hui
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Many kinases have been found to be intimately involved in oncogenesis and the deregulation of kinase function has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. Previously, we have performed gene expression profile analysis on HCC samples and have identified a host of kinases that are remarkably overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase (MELK) is highly overexpressed in HCC and its overexpression strongly correlates with early recurrence and poor patients' survival...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27680505/the-possible-roles-of-b-cell-novel-protein-1-bcnp1-in-cellular-signalling-pathways-and-in-cancer
#19
Sapan J Patel, Gaurang L Trivedi, Costel C Darie, Bayard D Clarkson
B-cell novel protein-1 (BCNP1) or Family member of 129C (FAM129C) was identified as a B-cell-specific plasma-membrane protein. Bioinformatics analysis predicted that BCNP1 might be heavily phosphorylated. The BCNP1 protein contains a pleckstrin homology (PH) domain, two proline-rich (PR) regions and a Leucine Zipper (LZ) domain suggesting that it may be involved in protein-protein interactions. Using The Cancer Genome Atlas (TCGA) data sets, we investigated the correlation of alteration of the BCNP1 copy-number changes and mutations in several cancer types...
March 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27643134/sy-15-4-role-of-histone-deacetylases-in-regulating-endothelial-and-vascular-function
#20
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
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