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https://www.readbyqxmd.com/read/27534532/isoproterenol-increases-histone-deacetylase-6-expression-and-cell-migration-by-inhibiting-erk-signaling-via-pka-and-epac-pathways-in-human-lung-cancer-cells
#1
Jeong Ah Lim, Yong-Sung Juhnn
Stress conditions are correlated with tumor growth, progression and metastasis. We hypothesized that stress signals might affect tumor progression via epigenetic control of gene expression and investigated the effects of stress signals on the expression levels of histone deacetylases (HDACs) and the underlying mechanisms of these effects in lung cancer cells. Treatment with isoproterenol (ISO), an analog of the stress signal epinephrine, increased the expression of HDAC6 protein and mRNA in H1299 lung cancer cells...
2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27208785/overexpression-of-hdac6-induces-pro-inflammatory-responses-by-regulating-ros-mapk-nf-%C3%AE%C2%BAb-ap-1-signaling-pathways-in-macrophages
#2
Gi Soo Youn, Keun Wook Lee, Soo Young Choi, Jinseu Park
Although histone deacetylase 6 (HDAC6) has been implicated in inflammatory diseases, direct involvement and its action mechanism of HDAC6 in the transcriptional regulation of pro-inflammatory genes have been unclear. In this study, we investigated the possible role of HDAC6 in the expression of pro-inflammatory mediators, indicator of macrophage activation, in RAW 264.7 cells and primary mouse macrophages. HDAC6 overexpression significantly enhanced expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, with concomitant reduction in acetylated α-tubulin...
August 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26790818/tubastatin-a-an-hdac6-inhibitor-alleviates-stroke-induced-brain-infarction-and-functional-deficits-potential-roles-of-%C3%AE-tubulin-acetylation-and-fgf-21-up-regulation
#3
Zhifei Wang, Yan Leng, Junyu Wang, Hsiao-Mei Liao, Joel Bergman, Peter Leeds, Alan Kozikowski, De-Maw Chuang
Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as α-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction, and ameliorated neuronal cell death in MCAO rats...
January 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26783207/the-shp2-induced-epithelial-disorganization-defect-is-reversed-by-hdac6-inhibition-independent-of-cdc42
#4
Sui-Chih Tien, Hsiao-Hui Lee, Ya-Chi Yang, Miao-Hsia Lin, Yu-Ju Chen, Zee-Fen Chang
Regulation of Shp2, a tyrosine phosphatase, critically influences the development of various diseases. Its role in epithelial lumenogenesis is not clear. Here we show that oncogenic Shp2 dephosphorylates Tuba to decrease Cdc42 activation, leading to the abnormal multi-lumen formation of epithelial cells. HDAC6 suppression reverses oncogenic Shp2-induced multiple apical domains and spindle mis-orientation during division in cysts to acquire normal lumenogenesis. Intriguingly, Cdc42 activity is not restored in this rescued process...
2016: Nature Communications
https://www.readbyqxmd.com/read/26462017/molecular-mechanisms-underlying-the-antitumor-activity-of-e-n-hydroxy-3-1-4-methoxyphenylsulfonyl-1-2-3-4-tetrahydroquinolin-6-yl-acrylamide-in-human-colorectal-cancer-cells-in-vitro-and-in-vivo
#5
Chun-Han Chen, Chia-Hwa Lee, Jing-Ping Liou, Che-Ming Teng, Shiow-Lin Pan
Upregulation of class I histone deacetylases (HDAC) correlates with poor prognosis in colorectal cancer (CRC) patients. Previous study revealed that (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (Compound 11) is a potent and selective class I HDAC inhibitor, exhibited significant anti-proliferative activity in various human cancer cell lines. In current study, we demonstrated that compound 11 exhibited significant anti-proliferative and cytotoxic activity in CRC cells...
November 3, 2015: Oncotarget
https://www.readbyqxmd.com/read/26080397/nuclear-matrix-associated-protein-smar1-regulates-alternative-splicing-via-hdac6-mediated-deacetylation-of-sam68
#6
Kiran Kumar Nakka, Nidhi Chaudhary, Shruti Joshi, Jyotsna Bhat, Kulwant Singh, Subhrangsu Chatterjee, Renu Malhotra, Abhijit De, Manas Kumar Santra, F Jeffrey Dilworth, Samit Chattopadhyay
Pre-mRNA splicing is a complex regulatory nexus modulated by various trans-factors and their posttranslational modifications to create a dynamic transcriptome through alternative splicing. Signal-induced phosphorylation and dephosphorylation of trans-factors are known to regulate alternative splicing. However, the role of other posttranslational modifications, such as deacetylation/acetylation, methylation, and ubiquitination, that could modulate alternative splicing in either a signal-dependent or -independent manner remain enigmatic...
June 30, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26031809/hdac6-mediates-hiv-1-tat-induced-proinflammatory-responses-by-regulating-mapk-nf-kappab-ap-1-pathways-in-astrocytes
#7
Gi Soo Youn, Sung Mi Ju, Soo Young Choi, Jinseu Park
Human immunodeficiency virus (HIV)-1 transactivator of transcription (Tat) is a viral protein that induces extensive neuroinflammation by up-regulating proinflammatory mediators, including cytokines, chemokines, and adhesion molecules. Histone deacetylase 6 (HDAC6) has been implicated in the transcriptional regulation of inflammatory genes. In this study, we investigated the possible role of HDAC6 in HIV-1 Tat-induced up-regulation of proinflammatory mediators in astrocytes. HIV-1 Tat augmented HDAC6 expression, which was correlated with a reduction in acetylated α-tubulin in CRT-MG human astroglioma cells and primary mouse astrocytes...
June 1, 2015: Glia
https://www.readbyqxmd.com/read/25967390/preclinical-and-clinical-studies-of-the-nedd9-scaffold-protein-in-cancer-and-other-diseases
#8
REVIEW
Elena Shagisultanova, Anna V Gaponova, Rashid Gabbasov, Emmanuelle Nicolas, Erica A Golemis
Cancer progression requires a significant reprogramming of cellular signaling to support the essential tumor-specific processes that include hyperproliferation, invasion (for solid tumors) and survival of metastatic colonies. NEDD9 (also known as CasL and HEF1) encodes a multi-domain scaffolding protein that assembles signaling complexes regulating multiple cellular processes relevant to cancer. These include responsiveness to signals emanating from the T and B cell receptors, integrins, chemokine receptors, and receptor tyrosine kinases, as well as cytoplasmic oncogenes such as BCR-ABL and FAK- and SRC-family kinases...
August 1, 2015: Gene
https://www.readbyqxmd.com/read/25746105/hdac6-dependent-functions-in-tumor-cells-crossroad-with-the-mapk-pathways
#9
REVIEW
Joshua Haakenson, Jheng-Yu Wu, Shengyan Xiang, Kendra A Williams, Wenlong Bai, Xiaohong Zhang
Histone deacetylase 6 (HDAC6) is emerging as a novel therapeutic target in cancer treatment. HDAC6 plays an important role in cell migration, cell transformation, and DNA damage response. Our and others' studies have linked HDAC6's functions and HDAC6's regulation to the mitogen-activated protein kinase (MAPK) pathways. In particular, HDAC6's activity has been found to be regulated by EGF-EGFR-Ras-Raf-MEK-ERK signaling. Inversely, HDAC6 has been reported to modulate the functions of EGFR and Ras. In this review, we summarize the literature on HDAC6 and MAPK pathways, and emphasize the interaction between HDAC6 and the ERK-MAPK signaling cascade...
2015: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/25060902/ellagic-acid-inhibits-vegf-vegfr2-pi3k-akt-and-mapk-signaling-cascades-in-the-hamster-cheek-pouch-carcinogenesis-model
#10
Jaganathan Kowshik, Hemant Giri, Tanagala Kranthi Kiran Kishore, Rushendhiran Kesavan, Raju Naik Vankudavath, Geereddy Bhanuprakash Reddy, Madhulika Dixit, Siddavaram Nagini
BACKGROUND: Blocking vascular endothelial growth factor (VEGF) mediated tumor angiogenesis by phytochemicals has emerged as an attractive strategy for cancer prevention and therapy. METHODS: We investigated the anti-angiogenic effects of ellagic acid in a hamster model of oral oncogenesis by examining the transcript and protein expression of hypoxia-inducible factor-1alpha (HIF-1α), VEGF, VEGFR2, and the members of the PI3K/Akt and MAPK signaling cascades. Molecular docking studies and cell culture experiments with the endothelial cell line ECV304 were performed to delineate the mechanism by which ellagic acid regulates VEGF signaling...
2014: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/24227760/histone-deacetylase-inhibitors-with-enhanced-enzymatic-inhibition-effects-and-potent-in-vitro-and-in-vivo-antitumor-activities
#11
Lei Zhang, Yingjie Zhang, C James Chou, Elizabeth S Inks, Xuejian Wang, Xiaoguang Li, Jinning Hou, Wenfang Xu
In the present work, a series of small molecules were designed and synthesized based on structural optimization. A significant improvement in the enzyme inhibitory activity of these compounds was discovered. Moreover, the tested compounds have moderate preference for class I HDACs over HDAC6, as demonstrated by enzyme selectivity assays. In vitro antiproliferation assay results show that representative compounds can selectively inhibit the growth of non-solid lymphoma and leukemic cells such as U937, K562, and HL60...
March 2014: ChemMedChem
https://www.readbyqxmd.com/read/24089523/extracellular-signal-regulated-kinase-erk-phosphorylates-histone-deacetylase-6-hdac6-at-serine-1035-to-stimulate-cell-migration
#12
Kendra A Williams, Mu Zhang, Shengyan Xiang, Chen Hu, Jheng-Yu Wu, Shengping Zhang, Meagan Ryan, Adrienne D Cox, Channing J Der, Bin Fang, John Koomen, Eric Haura, Gerold Bepler, Santo V Nicosia, Patrick Matthias, Chuangui Wang, Wenlong Bai, Xiaohong Zhang
Histone deacetylase 6 (HDAC6) is well known for its ability to promote cell migration through deacetylation of its cytoplasmic substrates such as α-tubulin. However, how HDAC6 itself is regulated to control cell motility remains elusive. Previous studies have shown that one third of extracellular signal-regulated kinase (ERK) is associated with the microtubule cytoskeleton in cells. Yet, no connection between HDAC6 and ERK has been discovered. Here, for the first time, we reveal that ERK binds to and phosphorylates HDAC6 to promote cell migration via deacetylation of α-tubulin...
November 15, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24023871/the-hdac-inhibitor-lbh589-induces-erk-dependent-prometaphase-arrest-in-prostate-cancer-via-hdac6-inactivation-and-down-regulation
#13
Mei-Jen Chuang, Sheng-Tang Wu, Shou-Hung Tang, Xiang-Me Lai, Hsiao-Chu Lai, Kai-Hsiang Hsu, Kuang-Hui Sun, Guang-Huan Sun, Sun-Yran Chang, Dah-Shyong Yu, Pei-Wen Hsiao, Shih-Ming Huang, Tai-Lung Cha
Histone deacetylase inhibitors (HDACIs) have potent anti-cancer activity in a variety of cancer models. Understanding the molecular mechanisms involved in the therapeutic responsiveness of HDACI is needed before its clinical application. This study aimed to determine if a potent HDACI, LBH589 (Panobinostat), had differential therapeutic responsiveness towards LNCaP and PC-3 prostate cancer (PCa) cells. The former showed prometaphase arrest with subsequent apoptosis upon LBH589 treatment, while the latter was less sensitive and had late G2 arrest...
2013: PloS One
https://www.readbyqxmd.com/read/23770849/oncogenic-shp2-disturbs-microtubule-regulation-to-cause-hdac6-dependent-erk-hyperactivation
#14
S-C Tien, Z-F Chang
Deregulation of Shp2, a non-receptor tyrosine phosphatase, causes hyperactivation of extracellular signal-regulated kinase (ERK), leading to growth abnormality. Here, we show that inhibition of RhoA-Dia is sufficient to upregulate ERK activation in epithelial cells. Oncogenic Shp2 expression attenuates RhoA-Dia signaling, by which microtubule (MT) is destabilized with reduced level of acetylation. Either MT stabilization, silencing of histone deacetylase 6 (HDAC6) or enforcing RhoA-Dia signal prevents oncogenic Shp2-induced ERK hyperactivation...
May 29, 2014: Oncogene
https://www.readbyqxmd.com/read/23444400/eb1-p150glued-and-clasp1-control-endothelial-tubulogenesis-through-microtubule-assembly-acetylation-and-apical-polarization
#15
Dae Joong Kim, Luis A Martinez-Lemus, George E Davis
Vascular tube morphogenesis requires the establishment of endothelial cell (EC) apical-basal polarity in three-dimensional (3D) extracellular matrices. To date, there is little understanding of how EC polarity is controlled during these highly dynamic and rapid morphogenic events. We show that the microtubule tip complex proteins, end binding 1 (EB1), p150(Glued), and Clasp1, control human EC tube formation by (1) inducing microtubule assembly and asymmetric cytoskeletal polarization, whereby acetylated and detyrosinated tubulins distribute in a subapical membrane location and filamentous actin distributes basally; (2) increasing tubulin posttranslational modifications, including required acetylation events; and (3) regulating an EC lumen signaling cascade that involves membrane type 1 matrix metallopatrinase (MT1-MMP)-dependent proteolysis as well as Pak, Raf, and Erk kinases...
April 25, 2013: Blood
https://www.readbyqxmd.com/read/22047054/a-novel-class-of-small-molecule-inhibitors-of-hdac6
#16
Elizabeth S Inks, Benjamin J Josey, Sean R Jesinkey, C James Chou
Histone deacetylases (HDACs) are a family of enzymes that play significant roles in numerous biological processes and diseases. HDACs are best known for their repressive influence on gene transcription through histone deacetylation. Mapping of nonhistone acetylated proteins and acetylation-modifying enzymes involved in various cellular pathways has shown protein acetylation/deacetylation also plays key roles in a variety of cellular processes including RNA splicing, nuclear transport, and cytoskeletal remodeling...
February 17, 2012: ACS Chemical Biology
https://www.readbyqxmd.com/read/19329208/epigenetic-modulation-of-radiation-response-in-human-cancer-cells-with-activated-egfr-or-her-2-signaling-potential-role-of-histone-deacetylase-6
#17
In Ah Kim, Mina No, Jang Mi Lee, Jin Hee Shin, Jee Sun Oh, Eun Jung Choi, Il Han Kim, Peter Atadja, Eric J Bernhard
BACKGROUND AND PURPOSE: Histone deacetylase inhibitors (HDIs) are prototypes of agents targeting epigenetic modifications and have received considerable attention for their promise as targeted anticancer drugs. We examined the effects and potential mechanism(s) of combining LBH589 and irradiation in human cancer cells having activated EGFR or HER-2 signaling, focusing on the role of HDAC6. METHODS AND MATERIALS: We evaluated whether the HDI, LBH589, would radiosensitize a panel of human tumor cell lines having activated EGFR or HER-2 signaling...
July 2009: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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