Search results for "histone acetyltransferases"
showing 10 items of 44 documents
Redox signaling and histone acetylation in acute pancreatitis
2011
Histone acetylation via CBP/p300 coordinates the expression of proinflammatory cytokines in the activation phase of inflammation, particularly through mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducers and activators of transcription (STAT) pathways. In contrast, histone deacetylases (HDACs) and protein phosphatases are mainly involved in the attenuation phase of inflammation. The role of reactive oxygen species (ROS) in the inflammatory cascade is much more important than expected. Mitochondrial ROS act as signal-transducing molecules that trigger proinflammatory cytokine production via inflammasome-independent and inflammasome-dependent pathways. …
Site specificity of yeast histone acetyltransferase B complex in vivo
2008
Saccharomyces cerevisiae Hat1, together with Hat2 and Hif1, forms the histone acetyltransferase B (HAT-B) complex. Previous studies performed with synthetic N-terminal histone H4 peptides found that whereas the HAT-B complex acetylates only Lys12, recombinant Hat1 is able to modify Lys12 and Lys5. Here we demonstrate that both Lys12 and Lys5 of soluble, non-chromatin-bound histone H4 are in vivo targets of acetylation for the yeast HAT-B enzyme. Moreover, coimmunoprecipitation assays revealed that Lys12/Lys5-acetylated histone H4 is bound to the HAT-B complex in the soluble cell fraction. Both Hat1 and Hat2, but not Hif1, are required for the Lys12/Lys5-specific acetylation and for histone …
Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells
2013
International audience; MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its …
Pentoxifylline Prevents Loss of PP2A Phosphatase Activity and Recruitment of Histone Acetyltransferases to Proinflammatory Genes in Acute Pancreatitis
2009
Mitogen-activated protein kinases (MAPKs) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of extracellular signal regulated kinase (ERK) phosphorylation and tumor necrosis factor alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as an anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and ERK kinase (MEK1/2), as well as PP2A, PP2B, and PP2C serine/threonine phosphatase activiti…
Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4alpha requires coactivators peroxisomal proliferator activated…
2006
Hepatocyte nuclear factor 4alpha (HNF4alpha) is a key transcription factor for the constitutive expression of cytochromes P450 (P450s) in the liver. However, human hepatoma HepG2 cells show a high level of HNF4alpha but express only marginal P450 levels. We found that the HNF4alpha-mediated P450 transcription in HepG2 is impaired by the low level of coactivators peroxisomal proliferator activated receptor-gamma coactivator 1alpha (PGC1alpha) and steroid receptor coactivator 1 (SRC1). Reporter assays with a chimeric CYP2C9-LUC construct demonstrated that the sole transfection of coactivators induced luciferase activity in HepG2 cells. In HeLa cells however, CYP2C9-LUC activity only significa…
MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish.
2008
The inv(8)(p11q13) chromosomal abnormality, described in acute myeloid leukaemias (AML), fuses the histone acetyl-transferase (HAT) MYST3 (MOZ) gene with another HAT gene, NCOA2 (TIF2). We generated a transgenic zebrafish in which the MYST3/NCOA2 fusion gene was expressed under control of the spi1 promoter. An AML developed in 2 of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after injection of the fusion gene in a one-cell embryo, respectively. This leukaemia was characterised by an extensive invasion of kidneys by myeloid blast cells. This model, which is the first zebrafish model of AML, demonstrates the oncogenic potency of MYST3/NCOA2 fusion gene.
Redox signaling in acute pancreatitis
2015
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…
Role of Redox Signaling, Protein Phosphatases and Histone Acetylation in the Inflammatory Cascade in Acute Pancreatitis: Therapeutic Implications
2010
Acute pancreatitis starts as a local inflammation of the pancreatic tissue but often leads to the systemic inflammatory response syndrome and death by multiple organ failure. Pro-inflammatory cytokines, particularly TNF-alpha and Il-1beta, play a pivotal role together with oxidative stress and glutathione depletion in the inflammatory response in this disease. Most inflammatory mediators act through mitogen activated protein kinases and nuclear factor kB. Nevertheless, elucidation of the precise mechanisms involved in activation and attenuation phases of the inflammatory cascade is still underway. Redox signaling mediated by inactivation of protein phosphatases and histone acetylation trigg…
Regulation of NADPH oxidase-mediated superoxide production by acetylation and deacetylation
2021
Oral treatment of apolipoprotein E-knockout (ApoE-KO) mice with the putative sirtuin 1 (SIRT1) activator resveratrol led to a reduction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in the heart. In contrast, the SIRT1 inhibitor EX527 enhanced the superoxide production in isolated human polymorphonuclear granulocytes. In human monocytic THP-1 cells, phorbol ester-stimulated superoxide production was enhanced by inhibitors of histone deacetylases (HDACs; including quisinostat, trichostatin A (TSA), PCI34051, and tubastatin A) and decreased by inhibitors of histone acetyltransferases [such as garcinol, curcumin, and histone acetyltransferase (HAT) Inhibitor II]. Thes…
Phosphorylation of Elp1 by Hrr25 is required for elongator-dependent tRNA modification in yeast.
2014
Elongator is a conserved protein complex comprising six different polypeptides that has been ascribed a wide range of functions, but which is now known to be required for modification of uridine residues in the wobble position of a subset of tRNAs in yeast, plants, worms and mammals. In previous work, we showed that Elongator's largest subunit (Elp1; also known as Iki3) was phosphorylated and implicated the yeast casein kinase I Hrr25 in Elongator function. Here we report identification of nine in vivo phosphorylation sites within Elp1 and show that four of these, clustered close to the Elp1 C-terminus and adjacent to a region that binds tRNA, are important for Elongator's tRNA modification…