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Transcription CBP

Chao Huang, Zhe Zhang, Lihan Chen, Hank W Lee, Marina K Ayrapetov, Ting C Zhao, Yimei Hao, Jinsong Gao, Chunzhang Yang, Gautam U Mehta, Zhengping Zhuang, Xiaoren Zhang, Guohong Hu, Y Eugene Chin
Post-translational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions: myristoylation of G2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylated an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane...
March 12, 2018: Cancer Research
Yuanyuan Tang, Joshua Berlind, Nirmala Mavila
BACKGROUND: The WNT-beta-catenin pathway is known to regulate cellular homeostasis during development and tissue regeneration. Activation of WNT signaling increases the stability of cytoplasmic beta-catenin and enhances its nuclear translocation. Nuclear beta-catenin function is regulated by transcriptional co-factors such as CREB binding protein (CBP) and p300. Hyper-activated WNT-beta-catenin signaling is associated with many cancers. However, its role in inducing stemness to liver cancer cells, its autoregulation and how it regulates tumor suppressor pathways are not well understood...
March 12, 2018: Cell Communication and Signaling: CCS
Yan Liang, Xuedan Chen, Yuanyuan Wu, Juan Li, Shixin Zhang, Kai Wang, Xingying Guan, Kang Yang, Yun Bai
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. Recently, lncRNA CASC9 was shown to be dysregulated in many cancer types, but the mechanisms whereby this occurs remain largely unknown. In this study, we found that CASC9 was significantly upregulated in ESCC tissues, with further analysis revealing that elevated CASC9 expression was associated with ESCC prognosis and metastasis. Furthermore, we found that CASC9 knockdown significantly repressed ESCC migration and invasion in vitro and metastasis in nude mice in vivo...
March 6, 2018: Cell Death and Differentiation
Dimitrios Tsitsipatis, Keshav Gopal, Holger Steinbrenner, Lars-Oliver Klotz
Hepatic production and release of metabolites, nutrients and micronutrient transporters is tightly regulated at the level of gene expression. In this regard, transcription factor FOXO1 modulates the expression of genes such as G6PC and SELENOP, encoding the catalytic subunit of glucose 6-phosphatase and the plasma selenium transporter selenoprotein P, respectively. Here, we analyzed the role of cysteine residues in FOXO1 in controlling its activity with respect to regulation of G6PC and SELENOP in HepG2 human hepatoma cells...
February 26, 2018: Free Radical Biology & Medicine
Xuejie Jiang, Po Yee Mak, Hong Mu, Duncan Mak, Steven Kornblau, Qi Zhang, Peter Ruvolo, Jared K Burks, Weiguo Zhang, Teresa McQueen, Rongqing Pan, Hongsheng Zhou, Marina Konopleva, Jorge E Cortes, Qifa Liu, Michael Andreeff, Bing Z Carter, Wenjing Tao
PURPOSE: Wnt/β-catenin signaling is required for leukemic stem cell function. FLT3 mutations are frequently observed in acute myeloid leukemia (AML). Anomalous FLT3 signaling increases β-catenin nuclear localization and transcriptional activity. FLT3 tyrosine kinase inhibitors (TKIs) are used clinically to treat FLT3-mutated AML patients, but with limited efficacy. We investigated the anti-leukemia activity of combined Wnt/β-catenin and FLT3 inhibition in FLT3-mutant AML. EXPERIMENTAL DESIGN: Wnt/β-catenin signaling was inhibited by the b-catenin/CBP antagonist C-82/PRI-724 or siRNAs, and FLT3 signaling by sorafenib or quizartinib...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xueying Li, Jiaqi Jin, Siyuan Yang, Weizhi Xu, Xianbin Meng, Haiteng Deng, Jun Zhan, Shan Gao, Hongquan Zhang
GATA3 is a transcriptional factor involved in the development of multiple organs. Post translational modifications of GATA3 are critical to its function. Here, we report that GATA3 interacts with and is acetylated by the acetyltransferase CBP. Class I deacetylases HDAC1, HDAC2 and HDAC3 deacetylate GATA3. The major acetylated site of GATA3 in lung adenocarcinoma cells was determined at lysine 119 (AcK119). Functionally, GATA3-acetylation mimics K119Q mutant was found to inhibit lung adenocarcinoma cell migration and invasion with concomitant downregulation of EMT-controlling transcriptional factors Slug, Zeb1 and Zeb2...
February 14, 2018: Biochemical and Biophysical Research Communications
Tyler J Lahusen, Seung-Jin Kim, Kai Miao, Zebin Huang, Xiaoling Xu, Chu-Xia Deng
Breast cancer associated gene 1 (BRCA1) function has been shown to be regulated by phosphorylation but the role of acetylation has not been determined. Therefore, we tested whether BRCA1 can be acetylated by the acetyltransferases P300/CBP-associated factor (pCAF), GCN5, and p300. p300 exhibited the highest level of BRCA1 acetylation; however, there was also a decrease in the total level of BRCA1. Therefore, we focused on pCAF and GCN5 because they both acetylated BRCA1 without affecting BRCA1 expression. Further analysis indicated that the acetylated form of BRCA1 is deacetylated by wild-type (WT) SIRT1, but not deacetylase mutant SIRT1, suggesting that SIRT1 is a specific deacetylase of BRCA1...
February 14, 2018: Oncogene
Octavio Silva-García, Rosa Rico-Mata, María Cristina Maldonado-Pichardo, Alejandro Bravo-Patiño, Juan J Valdez-Alarcón, Jorge Aguirre-González, Víctor M Baizabal-Aguirre
Glycogen synthase kinase 3 (GSK3) is a constitutive enzyme implicated in the regulation of cytokine expression and the inflammatory response during bacterial infections. Mammals have two GSK3 isoforms named GSK3α and GSK3β that plays different but often overlapping functions. Although the role of GSK3β in cytokine regulation during the inflammatory response caused by bacteria is well described, GSK3α has not been found to participate in this process. Therefore, we tested if GSK3α may act as a regulatory isoform in the cytokine expression by bovine endothelial cells infected with Staphylococcus aureus because this bacterium is one of the major pathogens that cause tissue damage associated with inflammatory dysfunction...
2018: Frontiers in Immunology
Clifford Thomas Gee, Keith E Arntson, Edward J Koleski, Rachel Lynn Staebell, William Charles Krause Pomerantz
Protein-Observed Fluorine NMR Spectroscopy (PrOF NMR) is an emerging technique for screening and characterizing small molecule-protein interactions. The choice of which amino acid to label for PrOF NMR can be critical for analysis. Here we report the first use of a protein containing two different fluoroaromatic amino acids for NMR studies. Using the KIX domain of the CBP/p300 as a model system, we examine ligand binding of several small molecules elaborated from our previous fragment screen and identify a new ligand binding site distinct from those used by native transcription factors...
February 11, 2018: Chembiochem: a European Journal of Chemical Biology
Fernanda Bajanca, Laurence Vandel
Histone acetyl transferases (HATs) and histone deacetylases (HDAC) control transcription during myogenesis. HDACs promote chromatin condensation, inhibiting gene transcription in muscle progenitor cells until myoblast differentiation is triggered and HDACs are released. HATs, namely CBP/p300, activate myogenic regulatory and elongation factors promoting myogenesis. HDAC inhibitors are known to improve regeneration in dystrophic muscles through follistatin upregulation. However, the potential of directly modulating HATs remains unexplored...
December 21, 2017: PLoS Currents
Swaathi Jayaraman, Michele Doucet, Scott L Kominsky
The transcriptional co-regulator Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain-2 (CITED2) may promote breast tumor growth; however, the mechanisms by which its effects are mediated remain to be fully elucidated. Tumor-associated macrophages serve an important function in tumor development and progression and are recruited by chemotactic factors produced by cells within the tumor microenvironment. The present study assessed the effects of CITED2 silencing on macrophage recruitment in two xenograft mouse models of human breast cancer, one in which tumor growth was sensitive to CITED2 silencing (MDA-MB-231) and one in which it was insensitive (MDA-MB-468)...
January 2018: Oncology Letters
M Yu Mazina, P K Derevyanko, E V Kocheryzhkina, Yu V Nikolenko, A N Krasnov, N E Vorobyeva
The objective of this study was to identify transcriptional coactivators participating in transcription elongation of the hsp70 gene induced by heat shock. We found that all investigated coactivator complexes participate in transcription of this gene, as significant level of them were present at the gene promoter in its active state. For most of the coactivators (except for p300/CBP, Set2, and Mediator complex), we also observed a considerable increase of their binding level at the coding region of the gene after activation of its transcription by heat shock...
February 2017: Genetika
Jingjing Xu, Amit Roy, Subba Reddy Palli
Juvenile hormones (JH) and ecdysteroids regulate many biological and metabolic processes. CREB-binding protein (CBP) is a transcriptional co-regulator with histone acetyltransferase (HAT) activity. Therefore, CBP is involved in activation of many transcription factors that regulate expression of genes associated with postembryonic development in insects. However, the function of CBP in JH action in insects is not well understood. Hence, we studied the role of CBP in JH action in the red flour beetle, Tribolium castaneum and the Tribolium cell line...
January 23, 2018: Scientific Reports
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
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
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
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
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 mitogen-activated protein kinase 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...
February 9, 2018: Journal of Biological Chemistry
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
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 β-cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for β-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 α- and β-cell area and islet insulin content...
March 2018: Diabetes
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