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https://www.readbyqxmd.com/read/29317678/peptidomimetic-blockade-of-myb-in-acute-myeloid-leukemia
#1
Kavitha Ramaswamy, Lauren Forbes, Gerard Minuesa, Tatyana Gindin, Fiona Brown, Michael G Kharas, Andrei V Krivtsov, Scott A Armstrong, Eric Still, Elisa de Stanchina, Birgit Knoechel, Richard Koche, Alex Kentsis
Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells. Treatment of AML cells with MYBMIM led to the dissociation of the MYB:CBP/P300 complex in cells, its displacement from oncogenic enhancers enriched for MYB binding sites, and downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29284404/multiple-functions-of-creb-binding-protein-during-postembryonic-development-identification-of-target-genes
#2
Amit Roy, Smitha George, Subba Reddy Palli
BACKGROUND: Juvenile hormones (JH) and ecdysteroids control postembryonic development in insects. They serve as valuable targets for pest management. Hence, understanding the molecular mechanisms of their action is of crucial importance. CREB-binding protein (CBP) is a universal transcriptional co-regulator. It controls the expression of several genes including those from hormone signaling pathways through co-activation of many transcription factors. However, the role of CBP during postembryonic development in insects is not well understood...
December 29, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29281714/coordinate-regulation-of-stress-signaling-and-epigenetic-events-by-acss2-and-hif-2-in-cancer-cells
#3
Rui Chen, Min Xu, Jason Nagati, Joseph A Garcia
Survival of cancer cells in the harsh tumor microenvironment, characterized by oxygen and glucose deprivation, requires rapid initiation of cytoprotective measures. Metabolites whose levels change during stress are ideal signaling cues, particularly if used in post-translational modifications of stress-responsive signal transducers. In cancer cells exposed to oxygen or glucose deprivation, there is an increase in cellular levels of acetate, a substrate for acetate-dependent acetyl CoA synthetase 2 (Acss2) that also stimulates translocation of Acss2 from the cytosol to the nucleus...
2017: PloS One
https://www.readbyqxmd.com/read/29274289/epigenetic-regulation-of-integrin-%C3%AE-6-transcription-induced-by-tgf-%C3%AE-1-in-human-oral-squamous-cell-carcinoma-cells
#4
Mingyan Xu, Liqin Yin, Yihuang Cai, Qingwei Hu, Jie Huang, Qing Ji, Yanping Hu, Wenxia Huang, Fan Liu, Songlin Shi, Xiaoling Deng
Overexpression of integrin αvβ6 is believed to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). However, little is known about the molecular mechanisms leading to αvβ6 upregualtion in OSCC. As the integrin β6 (ITGB6) is the only partner with αv, the expression of αvβ6 is dependent on ITGB6, it is therefore pivotal to investigate the mechanisms underlying ITGB6 overexpression in OSCC. We previously reported the cloning and characterization of human ITGB6 gene...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29259132/histone-deacetylase-6-hdac6-deacetylates-extracellular-signal-regulated-kinase-1-erk1-and-thereby-stimulates-erk1-activity
#5
Jheng-Yu Wu, Shengyan Xiang, Mu Zhang, Bin Fang, He Huang, Oh Kwang Kwon, Yingming Zhao, Zhe Yang, Wenlong Bai, Gerold Bepler, Xiaohong Mary Zhang
Histone deacetylase 6 (HDAC6), a class IIb HDAC, plays an important role in many biological and pathological processes. Previously, we found that ERK1, a downstream kinase in the MAPK signaling pathway, phosphorylates HDAC6, thereby increasing HDAC6-mediated deacetylation of α-tubulin. However, whether HDAC6 reciprocally modulates ERK1 activity is unknown. Here, we report that both ERK1 and 2 are acetylated and that HDAC6 promotes ERK1 activity via deacetylation. Briefly, we found that both ERK1 and 2 physically interact with HDAC6...
December 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29248490/acetylation-regulates-the-mkk4-jnk-pathway-in-t-cell-receptor-signaling
#6
Yukihide Matsui, Taku Kuwabara, Toyonobu Eguchi, Koichi Nakajima, Motonari Kondo
T cell functions are regulated by multiple signaling cascades, including the MKK4-JNK (c-Jun NH2 terminal kinase) pathway. However, the mechanism regulating the MKK4-JNK axis in T cells remains unclear. Herein, we demonstrated that protein acetylation modulates JNK activity induced by T cell receptor (TCR) activation. The acetyltransferase, CREB-binding protein (CBP), is transported from the nucleus to the cytoplasm in response to TCR cross-linking. To investigate the role of CBP in TCR signaling, we overexpressed CBP in the cytoplasm of Jurkat cells, a human T lymphocyte line...
December 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29217654/the-p300-and-cbp-transcriptional-coactivators-are-required-for-beta-cell-and-alpha-cell-proliferation
#7
Chi Kin Wong, Adam K Wade-Vallance, Dan S Luciani, Paul K Brindle, Francis C Lynn, William T Gibson
p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone acetyltransferase activity. Various beta cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for beta cell function and health in vivo We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced alpha and beta cell area and islet insulin content...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29217191/tnf-%C3%AE-induces-expression-of-the-circadian-clock-gene-bmal1-via-dual-calcium-dependent-pathways-in-rheumatoid-synovial-cells
#8
Kohsuke Yoshida, Ayako Nakai, Kenta Kaneshiro, Naonori Hashimoto, Kohjin Suzuki, Koto Uchida, Teppei Hashimoto, Yoshiko Kawasaki, Koji Tateishi, Natsuko Nakagawa, Nao Shibanuma, Yoshitada Sakai, Akira Hashiramoto
Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca2+ chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29207655/egr-1-regulates-rta-transcription-through-a-cooperative-involvement-of-transcriptional-regulators
#9
Roni Sarkar, Subhash C Verma
Kaposi's sarcoma associated herpesvirus (KSHV) regulates the host cellular environment to establish life-long persistent infection by manipulating cellular signaling pathways, with approximately 1- 5% of cells undergoing lytic reactivation during the course of infection. Egr-1 (Early Growth Response Factor-1) is one such cellular transcription factor, which gets phosphorylated during the lytic phase of viral life cycle to perpetrate its function. This study demonstrates the mechanism of how Egr-1 mediates transcription of the immediate early gene, RTA (Replication and transcription activator), which is the lytic switch gene of KSHV...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29170789/crebbp-and-p300-lysine-acetyl-transferases-in-the-dna-damage-response
#10
REVIEW
Ilaria Dutto, Claudia Scalera, Ennio Prosperi
The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl transferases (KAT) belonging to the KAT3 family of proteins known to modify histones, as well as non-histone proteins, thereby regulating chromatin accessibility and transcription. Previous studies have indicated a tumor suppressor function for these enzymes. Recently, they have been found to acetylate key factors involved in DNA replication, and in different DNA repair processes, such as base excision repair, nucleotide excision repair, and non-homologous end joining...
November 23, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29158051/the-regulation-of-foxo1-and-its-role-in-disease-progression
#11
REVIEW
Ya-Qi Xing, Ang Li, Yang Yang, Xiao-Xia Li, Li-Nan Zhang, Hui-Cai Guo
Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic dysregulation are the basis of many diseases. Forkhead box transcription factor O1 (FOXO1) changes in response to cellular stimulation and maintains tissue homeostasis during the above-mentioned physiological and pathological processes. Substantial evidences indicate that FOXO1's function depends on the modulation of downstream targets such as apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29123506/challenges-and-advances-for-genetic-engineering-of-non-model-bacteria-and-uses-in-consolidated-bioprocessing
#12
REVIEW
Qiang Yan, Stephen S Fong
Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29097748/kixbase-a-comprehensive-web-resource-for-identification-and-exploration-of-kix-domains
#13
Archana Yadav, Jitendra K Thakur, Gitanjali Yadav
The KIX domain has emerged in the last two decades as a critical site of interaction for transcriptional assembly, regulation and gene expression. Discovered in 1994, this conserved, triple helical globular domain has been characterised in various coactivator proteins of yeast, mammals and plants, including the p300/CBP (a histone acetyl transferase), MED15 (a subunit of the mediator complex of RNA polymerase II), and RECQL5 helicases. In this work, we describe the first rigorous meta analysis of KIX domains across all forms of life, leading to the development of KIXBASE, a predictive web server and global repository for detection and analysis of KIX domains...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29084253/pivotal-role-for-the-escrt-ii-complex-subunit-eap30-snf8-in-irf3-dependent-innate-antiviral-defense
#14
Kattareeya Kumthip, Darong Yang, Nan L Li, Yunzhi Zhang, Meiyun Fan, Aarti Sethuraman, Kui Li
The activation of interferon (IFN)-regulatory factor-3 (IRF3), characterized by phosphorylation and nuclear translocation of the latent transcription factor, is central to initiating innate antiviral responses. Whereas much has been learned about the upstream pathways and signaling mechanisms leading to IRF3 activation, how activated IRF3 operates in the nucleus to control transcription of IFNs remains obscure. Here we identify EAP30 (a.k.a, SNF8/VPS22), an endosomal sorting complex required for transport (ESCRT)-II subunit, as an essential factor controlling IRF3-dependent antiviral defense...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29063118/-dream-a-multifunctional-transcriptional-regulator
#15
Zi-Bing Fu, Xu-Bo Duan, Li-Na Li, Xiao-Kang Lei, Ye Jiang, Chen Wang, Han-Xiao Xu, Yin-Lian Zhang, Jiao-Hua Jiang, Rui-Chao Chai, Xi-Hua Jia, Albert Cheung Hoi Yu
DREAM (downstream regulatory element antagonist modulator), Calsenilin and KChIP3 (potassium channel interacting protein 3) belong to the neuronal calcium sensor (NCS) superfamily, which transduces the intracellular calcium signaling into a variety of activities. They are encoded by the same gene locus, but have distinct subcellular locations. DREAM was first found to interact with DRE (downstream regulatory element) site in the vicinity of the promoter of prodynorphin gene to suppress gene transcription. Calcium can disassemble this interaction by binding reversibly to DREAM protein on its four EF-hand motifs...
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29056321/cbp-regulates-recruitment-and-release-of-promoter-proximal-rna-polymerase-ii
#16
Ann Boija, Dig Bijay Mahat, Aman Zare, Per-Henrik Holmqvist, Philge Philip, David J Meyers, Philip A Cole, John T Lis, Per Stenberg, Mattias Mannervik
Transcription activation involves RNA polymerase II (Pol II) recruitment and release from the promoter into productive elongation, but how specific chromatin regulators control these steps is unclear. Here, we identify a novel activity of the histone acetyltransferase p300/CREB-binding protein (CBP) in regulating promoter-proximal paused Pol II. We find that Drosophila CBP inhibition results in "dribbling" of Pol II from the pause site to positions further downstream but impedes transcription through the +1 nucleosome genome-wide...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29042928/long-non-coding-rna-ab209630-suppresses-cell-proliferation-and-metastasis-in-human-hepatocellular-carcinoma
#17
Teng Li, Yun Liu, Yanming Sun
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and the second most common cause of cancer-related mortalities. With a high potential for metastasis and recurrence, HCC is refractory to cure. The present study aimed to explore the role of a recent-discovered LncRNA, AB209630, in human HCC, in order to provide new insights useful for clinical HCC diagnosis and treatment. Reverse transcription-quantitative polymerase chain reaction was performed to examine the expression of AB209630 in clinical HCC samples and the adjacent non-cancerous tissues...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29018059/involvement-of-leptin-in-the-molecular-physiology-of-the-placenta
#18
Malena Schanton, Julieta Lorena Maymó, Antonio Pérez-Pérez, Victor Sanchez-Margalet, Cecilia Varone
Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia, and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells...
October 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28974455/melatonin-as-an-angiogenesis-inhibitor-to-combat-cancer-mechanistic-evidence
#19
REVIEW
Nasser Hashemi Goradel, Mohammad Hossein Asghari, Milad Moloudizargari, Babak Negahdari, Hamed Haghi-Aminjan, Mohammad Abdollahi
Melatonin, a pineal indolamine, participates in different body functions and is shown to possess diverse biological activities such as anti-tumor action. Angiogenesis inhibition is one of the mechanisms by which melatonin exerts its oncostatic effects. Increased angiogenesis is a major feature of tumor progression, thus angiogenesis inhibition is a critical step in cancer therapy. Melatonin employs a variety of mechanisms to target nutrients and oxygen supply to cancer cells. At the transcriptional level, hypoxia induced factor-1α (HIF-1α) and the genes under its control, such as vascular endothelial growth factor (VEGF) are the main targets of melatonin for inhibition of angiogenesis...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28953875/discovery-of-a-selective-catalytic-p300-cbp-inhibitor-that-targets-lineage-specific-tumours
#20
Loren M Lasko, Clarissa G Jakob, Rohinton P Edalji, Wei Qiu, Debra Montgomery, Enrico L Digiammarino, T Matt Hansen, Roberto M Risi, Robin Frey, Vlasios Manaves, Bailin Shaw, Mikkel Algire, Paul Hessler, Lloyd T Lam, Tamar Uziel, Emily Faivre, Debra Ferguson, Fritz G Buchanan, Ruth L Martin, Maricel Torrent, Gary G Chiang, Kannan Karukurichi, J William Langston, Brian T Weinert, Chunaram Choudhary, Peter de Vries, John H Van Drie, David McElligott, Ed Kesicki, Ronen Marmorstein, Chaohong Sun, Philip A Cole, Saul H Rosenberg, Michael R Michaelides, Albert Lai, Kenneth D Bromberg
The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer)...
October 5, 2017: Nature
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