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Leucine zipper kinase

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https://www.readbyqxmd.com/read/29790920/elucidating-the-role-of-the-maternal-embryonic-leucine-zipper-kinase-melk-in-adrenocortical-carcinoma
#1
Katja Kiseljak-Vassiliades, Yu Zhang, Adwitiya Kar, Raud Razzaghi, Mei Xu, Katherine Gowan, Christopher D Raeburn, Maria Albuja-Cruz, Kenneth L Jones, Hilary Somerset, Lauren Fishbein, Stephen Leong, Margaret E Wierman
Adrenocortical carcinoma (ACC) is an aggressive cancer with a five-year survival less than 35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified Maternal Embryonic Leucine Zipper Kinase (MELK) as 4.1-fold overexpressed in ACC compared to normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells...
May 21, 2018: Endocrinology
https://www.readbyqxmd.com/read/29783958/sanguinarine-triggers-intrinsic-apoptosis-to-suppress-colorectal-cancer-growth-through-disassociation-between-strap-and-melk
#2
Xianling Gong, Zhihong Chen, Qinrui Han, Chunhui Chen, Linlin Jing, Yawei Liu, Liang Zhao, Xueqing Yao, Xuegang Sun
BACKGROUND: Previous studies showed sanguinarine induced apoptosis in CRC cells but did not define the underlying mechanisms. The purpose of this work was to determine the in vivo and in vitro effects of sanguinarine on CRC tumors and to elucidate the mechanism in regulating the intrinsic apoptosis. METHODS: Cell viability of CRC cell lines treated with sanguinarine was measured by MTT assay. Apoptotic cells stained with Annexin V and 7-AAD were detected by flow cytometry...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29764979/the-complex-relationship-between-tfeb-transcription-factor-phosphorylation-and-subcellular-localization
#3
REVIEW
Rosa Puertollano, Shawn M Ferguson, James Brugarolas, Andrea Ballabio
The MiT-TFE family of basic helix-loop-helix leucine-zipper transcription factors includes four members: TFEB, TFE3, TFEC, and MITF Originally described as oncogenes, these factors play a major role as regulators of lysosome biogenesis, cellular energy homeostasis, and autophagy. An important mechanism by which these transcription factors are regulated involves their shuttling between the surface of lysosomes, the cytoplasm, and the nucleus. Such dynamic changes in subcellular localization occur in response to nutrient fluctuations and various forms of cell stress and are mediated by changes in the phosphorylation of multiple conserved amino acids...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29753743/jlp-jnk-signaling-protects-cancer-cells-from-reactive-oxygen-species-induced-cell-death
#4
Rong Li, I Ketut Gunarta, Ryusuke Suzuki, Jambaldorj Boldbaatar, Ryota Nakazato, Dewi Yuliana, Gantulga Davaakhuu, Tsendsuren Oyunsuren, Nobuhiko Takamatsu, Masahiko Kobayashi, Atsushi Hirao, Katsuji Yoshioka
Oxidative stress, which can be caused by an overproduction of reactive oxygen species (ROS), often leads to cell death. In recent years, c-Jun NH2 -terminal kinase (JNK)-associated leucine zipper protein (JLP, also known as SPAG9 or JIP4), a scaffold protein for JNK mitogen-activated protein kinase (MAPK) signaling pathways, was found to serve as a novel biomarker for cancer. However, although JNK MAPK pathways are reported to be activated in response to various stimuli, including oxidative stress, whether JLP is involved in ROS signaling remains unknown...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29748610/distinct-homeostatic-modulations-stabilize-reduced-postsynaptic-receptivity-in-response-to-presynaptic-dlk-signaling
#5
Pragya Goel, Dion Dickman
Synapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury. Although fundamental pathways that mediate intrinsic responses to neuronal injury have been defined, less is known about how synaptic partners adapt. We have investigated responses in the postsynaptic cell to presynaptic activation of the injury-related Dual Leucine Zipper Kinase pathway at the Drosophila neuromuscular junction. We find that the postsynaptic compartment reduces neurotransmitter receptor levels, thus depressing synaptic strength...
May 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29748441/maternal-embryonic-leucine-zipper-kinase-inhibitor-otssp167-has-preclinical-activity-on-multiple-myeloma-bone-disease
#6
Joséphine Muller, Arnold Bolomsky, Sophie Dubois, Elodie Duray, Kathrin Stangelberger, Erwan Plougonven, Margaux Lejeune, Angélique Léonard, Caroline Marty, Ute Hempel, Frédéric Baron, Yves Beguin, Martine Cohen-Solal, Heinz Ludwig, Roy Heusschen, Jo Caers
Multiple myeloma bone disease is characterized by an uncoupling of bone remodeling in the multiple myeloma microenvironment, resulting in the development of lytic bone lesions. Most myeloma patients suffer from these bone lesions, which not only causes morbidity but also negatively impacts survival. The development of novel therapies, ideally with a combined anti-resorptive and bone-anabolic effect, is of great interest because lesions persist with the current standard of care, even in patients in complete remission...
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29723221/impact-of-silencing-hepatic-srebp-1-on-insulin-signaling
#7
Victoria Jideonwo, Yongyong Hou, Miwon Ahn, Sneha Surendran, Núria Morral
Sterol Regulatory Element Binding Protein-1 (SREBP-1) is a conserved transcription factor of the basic helix-loop-helix leucine zipper family (bHLH-Zip) that plays a central role in regulating expression of genes of carbohydrate and fatty acid metabolism in the liver. SREBP-1 activity is essential for the control of insulin-induced anabolic processes during the fed state. In addition, SREBP-1 regulates expression of key molecules in the insulin signaling pathway, including insulin receptor substrate 2 (IRS2) and a subunit of the phosphatidylinositol 3-kinase (PI3K) complex, PIK3R3, suggesting that feedback mechanisms exist between SREBP-1 and this pathway...
2018: PloS One
https://www.readbyqxmd.com/read/29705396/acute-physical-exercise-increases-the-adaptor-protein-appl1-in-the-hypothalamus-of-obese-mice
#8
Rafael Calais Gaspar, Vitor Rosetto Muñoz, Guilherme Pedron Formigari, Gabriel Keine Kuga, Susana Castelo Branco Ramos Nakandakari, José Diego Botezelli, Adelino S R da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle, José Rodrigo Pauli
Adiponectin is considered an adipokine that has essential anti-inflammatory and insulin-sensitivity actions. The adaptor protein containing the pleckstrin homology domain, the phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a protein involved in adiponectin signaling that plays a role in many physiological and pathophysiological processes. In the central nervous system, adiponectin can potentiate the effects of leptin in the arcuate proopiomelanocortin (POMC) neurons. However, the role of APPL1 in the hypothalamus is not well understood...
April 26, 2018: Cytokine
https://www.readbyqxmd.com/read/29611645/expression-of-follicle-stimulating-hormone-receptor-fshr-protein-kinase-b-2-akt2-and-adapter-protein-with-ph-domain-ptb-domain-and-leucine-zipper-appl1-in-pig-ovaries
#9
Ning Zhou, Ning Wang, Xiang Qin, Qian Liu, Juhua Wang, Hui Dong, Jie Zhou, Fugui Fang
Follicle-stimulating hormone (FSH) regulates oogenesis and spermatogenesis by binding to its receptor (FSHR) on target cells in the ovary and testis, respectively. The signaling cascades activated after ligand binding are extremely complex and have been shown to include protein kinase A and phosphatidylinositol 3-kinase/protein kinase. The adapter protein APPL1 (adapter protein with PH domain, PTB domain, and leucine zipper), which is an assortment of other signaling proteins, was previously identified to interact with the FSH receptor (FSHR) and the protein kinase B (AKT) pathway...
December 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/29590625/leucine-zipper-bearing-kinase-is-a-critical-regulator-of-astrocyte-reactivity-in-the-adult-mammalian-cns
#10
Meifan Chen, Cédric G Geoffroy, Jessica M Meves, Aarti Narang, Yunbo Li, Mallorie T Nguyen, Vung S Khai, Xiangmei Kong, Christopher L Steinke, Krislyn I Carolino, Lucie Elzière, Mark P Goldberg, Yishi Jin, Binhai Zheng
Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29581254/a-zipped-helix-cap-potentiates-hamp-domain-control-of-chemoreceptor-signaling
#11
Caralyn E Flack, John S Parkinson
Environmental awareness is an essential attribute for all organisms. The chemotaxis system of Escherichia coli provides a powerful experimental model for the investigation of stimulus detection and signaling mechanisms at the molecular level. These bacteria sense chemical gradients with transmembrane proteins [methyl-accepting chemotaxis proteins (MCPs)] that have an extracellular ligand-binding domain and intracellular histidine kinases, adenylate cyclases, methyl-accepting proteins, and phosphatases (HAMP) and signaling domains that govern locomotor behavior...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29564697/the-wheat-tabzip2-transcription-factor-is-activated-by-the-nutrient-starvation-responsive-snrk3-cipk-protein-kinase
#12
Sukanya Luang, Pradeep Sornaraj, Natalia Bazanova, Wei Jia, Omid Eini, Syed Sarfraz Hussain, Nataliya Kovalchuk, Pradeep K Agarwal, Maria Hrmova, Sergiy Lopato
The understanding of roles of bZIP factors in biological processes during plant development and under abiotic stresses requires the detailed mechanistic knowledge of behaviour of TFs. Basic leucine zipper (bZIP) transcription factors (TFs) play key roles in the regulation of grain development and plant responses to abiotic stresses. We investigated the role and molecular mechanisms of function of the TabZIP2 gene isolated from drought-stressed wheat plants. Molecular characterisation of TabZIP2 and derived protein included analyses of gene expression and its target promoter, and the influence of interacting partners on the target promoter activation...
March 21, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29526794/role-of-sarm1-and-dr6-in-retinal-ganglion-cell-axonal-and-somal-degeneration-following-axonal-injury
#13
Kimberly A Fernandes, Katherine L Mitchell, Amit Patel, Olivia J Marola, Peter Shrager, Donald J Zack, Richard T Libby, Derek S Welsbie
Optic neuropathies such as glaucoma are characterized by the degeneration of retinal ganglion cells (RGCs) and the irreversible loss of vision. In these diseases, focal axon injury triggers a propagating axon degeneration and, eventually, cell death. Previous work by us and others identified dual leucine zipper kinase (DLK) and JUN N-terminal kinase (JNK) as key mediators of somal cell death signaling in RGCs following axonal injury. Moreover, others have shown that activation of the DLK/JNK pathway contributes to distal axonal degeneration in some neuronal subtypes and that this activation is dependent on the adaptor protein, sterile alpha and TIR motif containing 1 (SARM1)...
March 8, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29525129/the-c-s-1-bzip-network-a-regulatory-hub-orchestrating-plant-energy-homeostasis
#14
REVIEW
Wolfgang Dröge-Laser, Christoph Weiste
Sustaining energy homeostasis is crucial to every living being. To balance energy supply and demand, plants make use of an evolutionarily conserved management system consisting of two counteracting kinases, TOR (TARGET OF RAPAMYCIN) and SnRK1 (Snf1-RELATED PROTEIN KINASE 1). SnRK1 is involved in reorganizing enzymatic and transcriptional responses to survive energy-limiting conditions. Recently, members of the bZIP (basic leucine zipper) transcription factor family have been established as SnRK1 downstream mediators...
May 2018: Trends in Plant Science
https://www.readbyqxmd.com/read/29514046/resveratrol-stimulates-c-fos-gene-transcription-via-activation-of-erk1-2-involving-multiple-genetic-elements
#15
Gerald Thiel, Oliver G Rössler
The polyphenol resveratrol is found in many plant and fruits and is a constituent of our diet. Resveratrol has been proposed to have chemopreventive and anti-inflammatory activities. On the cellular level, resveratrol activates stimulus-regulated transcription factors. To identify resveratrol-responsive elements within a natural gene promoter, the molecular pathway leading to c-Fos gene expression by resveratrol was dissected. The c-Fos gene encodes a basic region leucine zipper transcription factor and is a prototype of an immediate-early gene that is regulated by a wide range of signaling molecules...
June 5, 2018: Gene
https://www.readbyqxmd.com/read/29498735/toward-universal-protein-post-translational-modification-detection-in-high-throughput-format
#16
Harri Härmä, Natalia Tong-Ochoa, Arjan J van Adrichem, Ilian Jelesarov, Krister Wennerberg, Kari Kopra
Post-translational modification (PTM) of proteins plays essential regulatory roles in a variety of pathological conditions. Reliable and practical assays are required to accelerate the discovery of inhibitors and activators for PTM related diseases. Today, methodologies are based on specific or group-specific PTM recognition of e.g. phosphate for kinase activity without extending to other type of PTMs. Here we have established a universal time-resolved luminescence assay on a peptide-break platform for the direct detection of wide variety of PTMs...
March 15, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29484383/the-transcription-factor-cmaf-is-targeted-by-mtor-and-regulates-the-inflammatory-response-via-the-tlr4-signaling-pathway
#17
Yan Wang, Caifu Luan, Guili Zhang, Chengming Sun
cMaf is a leucine-zipper transcription factor that is involved in cell differentiation, oncogenic transformation, and human diseases; however, the functions of cMaf in inflammatory responses in macrophages are still not fully understood. Western blot analysis showed that cMaf expression was induced by lipopolysaccharide (LPS) stimulation in mouse macrophages. An enzyme-linked immunosorbent assay was performed to detect the level of expression of inflammatory cytokines after knockdown of cMaf expression in macrophages using a small interfering RNA (siRNA)...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29483192/alternative-splicing-variant-of-the-scaffold-protein-appl1-suppresses-hepatic-adiponectin-signaling-and-function
#18
Amanda K Galan-Davila, Jiyoon Ryu, Kun Dong, Yang Xiao, Zhe Dai, Deling Zhang, Zhi Li, Amanda M Dick, Kevin D Liu, Amrita Kamat, Min Lu, Qunfeng Dong, Feng Liu, Lily Q Dong
Adiponectin is an adipocyte-derived hormone with antidiabetic activities that include increasing the sensitivity of cells to insulin. Adaptor protein containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif (APPL1) stimulates adiponectin signaling and promotes adiponectin's insulin-sensitizing effects by binding to two adiponectin receptors, AdipoR1 and AdipoR2, and the insulin receptor. In this study, we report an alternative splicing variant of APPL1 (APPL1sv) that is highly expressed in mouse liver, pancreas, and spleen tissues...
April 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29467389/long-glucocorticoid-induced-leucine-zipper-regulates-human-thyroid-cancer-cell-proliferation
#19
Emira Ayroldi, Maria Grazia Petrillo, Maria Cristina Marchetti, Lorenza Cannarile, Simona Ronchetti, Erika Ricci, Luigi Cari, Nicola Avenia, Sonia Moretti, Efisio Puxeddu, Carlo Riccardi
Long glucocorticoid-induced leucine zipper (L-GILZ) has recently been implicated in cancer cell proliferation. Here, we investigated its role in human thyroid cancer cells. L-GILZ protein was highly expressed in well-differentiated cancer cells from thyroid cancer patients and differentiated thyroid cancer cell lines, but poorly expressed in anaplastic tumors. A fusion protein containing L-GILZ, when overexpressed in an L-GILZ-deficient 8505C cell line derived from undifferentiated human thyroid cancer tissue, inhibited cellular proliferation in vitro...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29454832/identification-and-functional-analysis-of-inhibitor-of-nf-%C3%AE%C2%BAb-kinase-ikk-from-scylla-paramamosain-the-first-evidence-of-three-ikks-in-crab-species-and-their-expression-profiles-under-biotic-and-abiotic-stresses
#20
Mei Jiang, Dan-Dan Tu, Wen-Bin Gu, Yi-Lian Zhou, Qi-Hui Zhu, Xiao-Ling Guo, Miao-An Shu
IKK (inhibitor of NF-κB kinase) is the critical regulator for NF-κB (nuclear factor-κB) pathway against pathogenic invasion in vertebrates or invertebrates. However, the IKK from crab species has not yet been identified. In the present study, three full-length cDNA sequences of IKKs from mud crab Scylla paramamosain, designated as SpIKKβ, SpIKKε1 and SpIKKε2, were firstly cloned through RT-PCR and RACE methods. This is also the first report about the identification of two IKKε genes in mud crab and even in crustaceans...
July 2018: Developmental and Comparative Immunology
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