scholarly journals Activation of p53 Transcriptional Activity by SMRT: a Histone Deacetylase 3-Independent Function of a Transcriptional Corepressor

2014 ◽  
Vol 34 (7) ◽  
pp. 1246-1261 ◽  
Author(s):  
A. K. Adikesavan ◽  
S. Karmakar ◽  
P. Pardo ◽  
L. Wang ◽  
S. Liu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Activity ◽  
Independent Function ◽  
Transcriptional Corepressor ◽  
Histone Deacetylase 3

scholarly journals The Smad6-Histone Deacetylase 3 Complex Silences the Transcriptional Activity of the Glucocorticoid Receptor

2005 ◽  
Vol 280 (51) ◽  
pp. 42067-42077 ◽  
Author(s):  
Takamasa Ichijo ◽  
Antonis Voutetakis ◽  
Ana P. Cotrim ◽  
Nisan Bhattachryya ◽  
Makiko Fujii ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Histone Deacetylase ◽  
Transcriptional Activity ◽  
Histone Deacetylase 3

scholarly journals Histone Deacetylase 3 Associates With Key Regulators of NFκB Signaling in Lung Epithelial Cells Under Stimulation With LPS.

2021 ◽  
Author(s):  
Brent A Stanfield ◽  
Erik J Soderblom ◽  
Scott Palmer ◽  
Bruce Sullenger ◽  
Todd Purves ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Histone Deacetylase ◽  
Transcriptional Activity ◽  
Trichostatin A ◽  
Peptide Sequencing ◽  
Immune Defense ◽  
Lung Epithelial Cells ◽  
Mass Spectrometry Analysis ◽  
Activation Process ◽  
Histone Deacetylase 3

Abstract Introduction: Histone Deacetylase 3 (HDAC3) is a Class I member of the histone deacetylase family that is recruited to nuclear enhancers. HDAC3 is located within the cell nucleus, where it constitutes the sole endogenous HDAC interacting with the nuclear-receptor corepressor complex containing NCOR and SMRT (NCOR2). As such, HDAC3 has a unique role in modulating the transcriptional activity of nuclear receptors. We have previously demonstrated its involvement in the inflammatory response in Lipopolysaccharide A (LPS)-stimulated human MH-S alveolar macrophages in vitro, and its interaction with pro-inflammatory IL-12 and anti-inflammatory IL-10. Similarly, our previous work using the broad spectrum HDAC inhibitor trichostatin A has demonstrated therapeutic efficacy reducing the pathogenesis of acute gram negative pneumonia in-vivo. With the current project, we aim to identify the HDAC3 interactome in LPS-stimulated human pulmonary epithelial cells type II (A549), the first immune defense in pathogens invading the lungs. Methods: Human A549 cells were transfected with a BioID2-tagged HDAC3 plasmid, and were divided in three groups: a. Untreated, b. stimulated with LPS, and c. stimulated with LPS and treated with Entinostat (MS275, a HDAC1/3 inhibitor). Cells were lysed, and total and biotinylated protein were submitted for quantitative Liquid Chromatography/Mass Spectrometry analysis to identify the peptides that directly bind with HDAC3. Data were searched against the Swiss Protein Human database, and False Discovery Rate (FDR) was set at 1%. Results: The dataset yielded 395,776 peptide matches. After peptide sequencing by database searching and validation, and FDR exclusion, we identified 2,666 proteins. Of these, 33 have been annotated to function in the NF-kB signaling pathway and/or NF-kB-regulated transcriptional activity.Conclusion: Protein acetylation is a reversible post-translational modification that is known to stabilize protein structure and modify function and localization. With the current project we have identified several potential proteins in the HDAC3 interactome that may be targeted early in the NF-κB activation process to disrupt HDAC3-substrate interaction and potentially downstream signaling. Nuclear activation of NF-κB is known to be involved in the early stages of Acute Respiratory Distress Syndrome and is a target of intense study for the development of novel therapeutics.

scholarly journals Histone Deacetylase 3 and 4 Complex Stimulates the Transcriptional Activity of the Mineralocorticoid Receptor

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136801 ◽  
Author(s):  
Hae-Ahm Lee ◽  
Min-Ji Song ◽  
Young-Mi Seok ◽  
Seol-Hee Kang ◽  
Sang-Yeob Kim ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Mineralocorticoid Receptor ◽  
Transcriptional Activity ◽  
Histone Deacetylase 3

scholarly journals Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation

2010 ◽  
Vol 38 (14) ◽  
pp. 4607-4619 ◽  
Author(s):  
Dipanjan Chanda ◽  
Yuan-Bin Xie ◽  
Hueng-Sik Choi
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Corepressor

scholarly journals The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Li Ning ◽  
Xiong Rui ◽  
Wang Bo ◽  
Geng Qing
Keyword(s):  
Histone Deacetylase ◽  
Chromatin Remodeling ◽  
Current Knowledge ◽  
Organ Injury ◽  
Solid Organ ◽  
Solid Organ Injury ◽  
Histone Deacetylase 3 ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Therapeutic Value

AbstractHistone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.

scholarly journals Mutational Analysis of a Histone Deacetylase in Drosophila melanogaster: Missense Mutations Suppress Gene Silencing Associated With Position Effect Variegation

Genetics ◽  
2000 ◽  
Vol 154 (2) ◽  
pp. 657-668 ◽  
Author(s):  
Randy Mottus ◽  
Richard E Sobel ◽  
Thomas A Grigliatti
Keyword(s):  
Drosophila Melanogaster ◽  
Histone Deacetylase ◽  
Transcriptional Activity ◽  
Mutational Analysis ◽  
Position Effect ◽  
Transcriptional Regulator ◽  
Position Effect Variegation ◽  
Missense Mutations ◽  
Effect Variegation ◽  
New Mutations

Abstract For many years it has been noted that there is a correlation between acetylation of histones and an increase in transcriptional activity. One prediction, based on this correlation, is that hypomorphic or null mutations in histone deacetylase genes should lead to increased levels of histone acetylation and result in increased levels of transcription. It was therefore surprising when it was reported, in both yeast and fruit flies, that mutations that reduced or eliminated a histone deacetylase resulted in transcriptional silencing of genes subject to telomeric and heterochromatic position effect variegation (PEV). Here we report the first mutational analysis of a histone deacetylase in a multicellular eukaryote by examining six new mutations in HDAC1 of Drosophila melanogaster. We observed a suite of phenotypes accompanying the mutations consistent with the notion that HDAC1 acts as a global transcriptional regulator. However, in contrast to recent findings, here we report that specific missense mutations in the structural gene of HDAC1 suppress the silencing of genes subject to PEV. We propose that the missense mutations reported here are acting as antimorphic mutations that “poison” the deacetylase complex and propose a model that accounts for the various phenotypes associated with lesions in the deacetylase locus.

scholarly journals PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1425
Author(s):  
Alena Shmakova ◽  
Mark Frost ◽  
Michael Batie ◽  
Niall S. Kenneth ◽  
Sonia Rocha
Keyword(s):  
Protein Expression ◽  
Cellular Response ◽  
Transcriptional Activity ◽  
Mrna Translation ◽  
Protein Translation ◽  
Signalling Pathways ◽  
Independent Function ◽  
Protein Levels ◽  
Associated Proteins ◽  
Core Components

PBRM1, a component of the chromatin remodeller SWI/SNF, is often deleted or mutated in human cancers, most prominently in renal cancers. Core components of the SWI/SNF complex have been shown to be important for the cellular response to hypoxia. Here, we investigated how PBRM1 controls HIF-1α activity. We found that PBRM1 is required for HIF-1α transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1α mRNA translation, as absence of PBRM1 results in reduced actively translating HIF-1α mRNA. Interestingly, we found that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1α mRNA is m6A-modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1α mRNA and reduction of YTHDF2 results in reduced HIF-1α protein expression in cells. Our results identify a SWI/SNF-independent function for PBRM1, interacting with HIF-1α mRNA and the epitranscriptome machinery. Furthermore, our results suggest that the epitranscriptome-associated proteins play a role in the control of hypoxia signalling pathways.

scholarly journals Histone deacetylase 3 as a novel therapeutic target in multiple myeloma

Leukemia ◽  
2013 ◽  
Vol 28 (3) ◽  
pp. 680-689 ◽  
Author(s):  
J Minami ◽  
R Suzuki ◽  
R Mazitschek ◽  
G Gorgun ◽  
B Ghosh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Histone Deacetylase ◽  
Therapeutic Target ◽  
Histone Deacetylase 3 ◽  
Novel Therapeutic

scholarly journals miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

2014 ◽  
Vol 289 (40) ◽  
pp. 28019-28039 ◽  
Author(s):  
Youngmi Kim ◽  
Hyuna Kim ◽  
Hyunmi Park ◽  
Deokbum Park ◽  
Hansoo Lee ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Feedback Loop ◽  
Cancer Drugs ◽  
Histone Deacetylase 3 ◽  
Angiogenic Response ◽  
Anti Cancer
Sign in / Sign up

Export Citation Format

Share Document