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Proteomics study of HDAC6 silenced cells

ABSTRACT: The proteomic analysis here introduced was set up and performed to figure out global perturbations of the proteome of a breast cancer human cell line in the presence/absence of HDAC6 silencing.

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hcc-1806 Cell, Mammary Gland

DISEASE(S): Breast Cancer

SUBMITTER: Diego Sbardella

LAB HEAD: M.D. Ph.D. Diego Sbardella

PROVIDER: PXD054378 | Pride | 2024-10-17

REPOSITORIES: pride

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			Action	DRS
	CTRL1_1.raw	Raw
	CTRL1_2.raw	Raw
	CTRL2_1.raw	Raw
	CTRL2_2.raw	Raw
	HDAC6.mzid.gz	Mzid

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Publications

HDAC6 inhibition disrupts HDAC6-P300 interaction reshaping the cancer chromatin landscape.

Zamperla Michela Gottardi MG Illi Barbara B Barbi Veronica V Cencioni Chiara C Santoni Daniele D Gagliardi Stella S Garofalo Maria M Zingale Gabriele Antonio GA Pandino Irene I Sbardella Diego D Cipolla Lina L Sabbioneda Simone S Farsetti Antonella A Ripamonti Chiara C Fossati Gianluca G Steinkühler Christian C Gaetano Carlo C Atlante Sandra S

Clinical epigenetics 20240818 1

<h4>Background</h4>Histone deacetylases (HDACs) are crucial regulators of gene expression, DNA synthesis, and cellular processes, making them essential targets in cancer research. HDAC6, specifically, influences protein stability and chromatin dynamics. Despite HDAC6's potential therapeutic value, its exact role in gene regulation and chromatin remodeling needs further clarification. This study examines how HDAC6 inactivation influences lysine acetyltransferase P300 stabilization and subsequent ...[more]

PMID: 39155390

Similar Datasets

Hdac6 regulates Tip60-p400 function in stem cells (sequencing)

Project description:The Tip60 (also known as Kat5) lysine acetyltransferase functions broadly as a transcriptional co-activator that acetylates histones. In contrast, Tip60 functions in embryonic stem cells (ESCs) both to silence genes that promote differentiation and to activate genes required for proliferation. The mechanism by which Tip60 functions as a repressor is unknown. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs and is necessary for complete silencing of most differentiation genes targeted by Tip60. In contrast to differentiated cells, where Hdac6 is mainly cytoplasmic and does not interact with Tip60, Hdac6 is largely nuclear in ESCs and neural stem cells (NSCs) and interacts with Tip60-p400 in both cell types. Hdac6 is enriched at promoters bound by Tip60-p400 in ESCs, but while Tip60 binds on both sides of transcription start sites (TSSs), Hdac6 binding overlaps with only the downstream Tip60 peak. Surprisingly, Hdac6 does not deacetylate histones at these sites, but rather is required for Tip60 binding. These data suggest that nuclear exclusion of Hdac6 during differentiation plays a major role in modulation of Tip60-p400 function. We determined the genome-wide localization of Tip60 and Hdac6 in mouse ES cells, and examined genomic binding profiles of Tip60 and Hdac6 upon indicated knockdown by ChIP-seq. We examined genomic binding profiles of p400 upon indicated knockdown by ChIP-seq.

2013-11-20 | E-GEOD-42209 | biostudies-arrayexpress

Hdac6 regulates Tip60-p400 function in stem cells (sequencing)

2013-11-20 | GSE42209 | GEO

HDAC6 Inhibition Disrupts HDAC6-P300 Interaction Reshaping the Cancer Chromatin Landscape (ChIP-Seq)

Project description:Histone deacetylases (HDACs) are crucial regulators of gene expression, DNA synthesis, and cellular processes, making them essential targets in cancer research. HDAC6, specifically, influences protein stability and chromatin dynamics. Despite HDAC6's potential therapeutic value, its exact role in gene regulation and chromatin remodeling needs further clarification. This study examines how HDAC6 inactivation influences lysine acetyltransferase P300 stabilization and subsequent effects on chromatin structure and function in cancer cells. We employed the HDAC6 inhibitor ITF3756, siRNA, or CRISPR/Cas9 gene editing to inactivate HDAC6 in different epigenomic backgrounds. Constantly, this inactivation led to significant changes in chromatin accessibility, particularly increased acetylation of histone H3 lysines 9, 14, and 27 (ATAC-seq and H3K27Ac ChIP-seq analysis). Transcriptomics, proteomics, and gene ontology analysis revealed gene changes in cell proliferation, adhesion, migration, and apoptosis. Significantly, HDAC6 inactivation altered P300 ubiquitination, stabilizing P300 and leading to downregulating genes critical for cancer cell survival. Our study highlights the substantial impact of HDAC6 inactivation on the chromatin landscape of cancer cells and suggests a role for P300 in contributing to the anticancer effects. The stabilization of P300 with HDAC6 inhibition proposes a potential shift in therapeutic focus from HDAC6 itself to its interaction with P300. This finding opens new avenues for developing targeted cancer therapies, improving our understanding of epigenetic mechanisms in cancer cells.

2024-08-19 | GSE273645 | GEO

HDAC6 Inhibition Disrupts HDAC6-P300 Interaction Reshaping the Cancer Chromatin Landscape (ATAC-Seq)

2024-08-19 | GSE273644 | GEO

HDAC6 and HSP90 control the functions of Foxp3+ T regulatory cells

Project description:Foxp3+ T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3+ Tregs express histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression and protein function. Pan-HDAC inhibitors developed for oncology enhance Treg production and suppression but have limited non-oncologic applications given their broad effects. We show, using HDAC6-deficient mice and WT mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully MHC-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein, HSP90. Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of HDAC6 knock out, compared to wild type (C57BL6) control

2011-05-01 | E-GEOD-27896 | biostudies-arrayexpress

HDAC6 overexpression effect on mouse ESCs

Project description:Analysis of mouse ESCs overexpressing HDAC6. Histone deacetylase 6 (Hdac6) was discovered as a deacetylase of α-tubulin and functions in cell migration, immunity and resistance to virus infection in vitro. HDAC6 overexpression ESCs and control ESCs were selected for RNA extraction and hybridization on Agilent microarrays. Results provide insight into the role of HDAC6 in the mouse ESCs.

2016-12-01 | GSE81710 | GEO

Hdac6 is a stem-cell specific modulator of Tip60-p400 function (gene expression)

Project description:To identify the functional role of Hdac6 in embryonic stem cells, we examined gene expression changes in mouse ES cells upon Tip60, Hdac6 and double knockdown. Two biological replicates each for control (GFP), Tip60, Hdac6 and double KD in E14 mouse ESCs. Lentiviral-based shRNA was used and gene expression changes were determined 3 days after KD. The global gene expression profiles of Tip60, Hdac6 and double KD were compared to control KD cells.

2013-11-20 | E-GEOD-42208 | biostudies-arrayexpress

ARID1A-mutated ovarian cancers depend on HDAC6 activity

Project description:ARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most mutated epigenetic regulator in human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with ARID1A mutational status remain a challenge. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated ovarian tumors. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumors. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylated the Lysine 120 residue of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates p53’ apoptotic function by upregulating HDAC6. These results indicate that pharmacological inhibition of HDAC6 is a novel therapeutic strategy involving ARID1A-mutation

2017-07-14 | GSE84405 | GEO

HDAC6 interacting proteins under different stresses

Project description:we treated MFE cell (WT and HDAC6 KO) with different stresses, incluing MG132, CytoD and IAV infection, then use home-made HDAC6 antibody to capture HDAC6 and coimmunoprecipitate its interacting proteins.

2023-10-17 | PXD038816 | Pride

Network-based assessment of HDAC6 activity is highly predictive of pre-clinical and clinical responses to the HDAC6 inhibitor ricolinostat [array]

Project description:Despite the anticancer activity of pan-histone deacetylase (HDAC) inhibitors, their clinical use has been limited due to toxicity. However, the development of more specific inhibitors that selectively inhibit individual HDACs is emerging as a novel and well-tolerated alternative. Here, we present the results of the first clinical trial evaluating the activity of ricolinostat (the leading HDAC6 inhibitor) in breast cancer (BC) patients. We have developed a computational network-based algorithm to evaluate the activity of the HDAC6 protein, based on the enrichment of its transcriptional targets in differentially expressed genes (HDAC6 score). Through preclinical in vitro and in vivo studies, we confirmed that the HDAC6 score can stratify the sensitivity of BC cells to ricolinostat treatment and may thus have value as a predictive biomarker. Moreover, analysis of ~3,000 primary human breast cancers showed that ~30% of them present high HDAC6 scores. Based on these results, we designed a phase Ib clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in metastatic BC patients. Study results showed that the two agents can be safely combined, that clinical activity is identified specifically in patients with HR+/HER2- disease, and that the HDAC6 score was predictive of response. Expansion of our analysis to other tumor types identified multiple cohorts enriched in high HDAC6 score samples. These results suggest that the HDAC6 score may provide an effective predictive biomarker of ricolinostat sensitivity in multiple human cancers.

2023-02-09 | GSE180606 | GEO

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