Search results for "Phosphor"
showing 10 items of 1952 documents
In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- and Benzamide-Type Histone Deacetylase Inhibitors (HDACi)
2020
Histone deacetylase inhibitors (HDACi) are already approved for the therapy of leukemias. Since they are also emerging candidate compounds for the treatment of non-malignant diseases, HDACi with a wide therapeutic window and low hazard potential are desirable. Here, we investigated a panel of 12 novel hydroxamic acid- and benzamide-type HDACi employing non-malignant V79 hamster cells as toxicology guideline-conform in vitro model. HDACi causing a &ge
NLRP3 controls ATM activation in response to DNA damage
2020
The DNA damage response (DDR) is essential to preserve genomic integrity and acts as a barrier to cancer. The ATM pathway orchestrates the cellular response to DNA double strand breaks (DSBs), and its attenuation is frequent during tumorigenesis. Here, we show that NLRP3, a Pattern Recognition Receptor known for its role in the inflammasome complex formation, interacts with the ATM kinase to control the early phase of DDR, independently of its inflammasome activity. NLRP3 down-regulation in human bronchial epithelial cells impairs ATM pathway activation as shown by an altered ATM substrate phosphorylation profile, and due to impaired p53 activation, confers resistance to acute genomic stres…
DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis
2011
DNA damaging agents are potent inducers of cell death triggered by apoptosis. Since these agents induce a plethora of different DNA lesions, it is firstly important to identify the specific lesions responsible for initiating apoptosis before the apoptotic executing pathways can be elucidated. Here, we describe specific DNA lesions that have been identified as apoptosis triggers, their repair and the signaling provoked by them. We discuss methylating agents such as temozolomide, ionizing radiation and cisplatin, all of them are important in cancer therapy. We show that the potentially lethal events for the cell are O(6)-methylguanine adducts that are converted by mismatch repair into DNA dou…
Intracellular signal transduction pathways in sponges.
1990
Abstract Sponges are the lowest multicellular eukaryotic organisms. Due to the relatively low specialization, and concomitantly the high differentiation and dedifferentiation potency of their cells, the sponge cell system has proven to be a useful model to study the mechanism of cell-cell adhesion on molecular levels. Results of detailed biochemical and cell biological studies with the main cell adhesion molecules, the aggregation factor (AF) and the aggregation receptor, led to the formation of the modulation theory of cell adhesion. The events of cell adhesion are contigent on a multiplicity of precisely coordinated intracellular signal transduction pathways. Using the marine sponge Geodi…
Phosphorylation and DNA binding of the regulator DcuR of the fumarate-responsive two-component system DcuSR of Escherichia coli
2004
The function of the response regulator DcuR of the DcuSR fumarate two-component sensory system of Escherichia coli was analysed in vitro. Isolated DcuR protein was phosphorylated by the sensory histidine kinase, DcuS, and ATP, or by acetyl phosphate. In gel retardation assays with target promoters (frdA, dcuB, dctA), phosphoryl DcuR (DcuR-P) formed a high-affinity complex, with an apparent K D (app. K D) of 0·2–0·3 μM DcuR-P, and a low-affinity (app. K D 0·8–2 μM) complex. The high-affinity complex was formed only with promoters transcriptionally-regulated by DcuSR, whereas low-affinity binding was seen also with some DcuSR-independent promoters. The binding site of DcuR-P at the dcuB promo…
Molecular cloning and expression of Tenebrio molitor ultraspiracle during metamorphosis and in vivo induction of its phosphorylation by 20-hydroxyecd…
2000
Using a RT-PCR approach, the Tenebrio molitor homologue of Drosophila Ultraspiracle (TmUSP) was characterized. Its DNA binding domain shows a degree of identity with those of the other insect USPs. However, the ligand binding domain is closer to those of retinoid X receptors. Using an antibody raised against DmUSP, Western blot analysis of proteins from epidermis and other tissues revealed five immunoreactive bands, corresponding to different phosphorylated forms of a unique polypeptide, as shown by lambda-phosphatase treatment. The nuclear form of TmUSP seems unphosphorylated. An in vivo 20-hydroxyecdysone treatment increases considerably and rapidly the phosphorylated forms of TmUSP. This…
Overexpression and functional characterization of kinin receptors reveal subtype-specific phosphorylation.
1999
G protein-coupled receptors such as the receptors for bradykinin are present in low copy numbers in most natural cells. To overcome the problems associated with the analysis of these receptors at the protein level, we used highly efficient expression systems such as the baculovirus/insect cell system. However, the structural and functional statuses of recombinant receptors have often remained elusive. We have expressed the two types of human kinin receptors, B1 and B2, in Sf9 cells. Both receptors are found on the surface of infected cells where they display the same pharmacological profiles as their cognate receptors of native cells. The functional analysis of kinin receptors coupled to th…
Lack of phosphoserine phosphatase activity alters pollen and tapetum development in Arabidopsis thaliana.
2015
Formation of mature pollen grain, an essential process for the reproduction of higher plants, is affected in lines that are deficient in the enzymes of the phosphorylated pathway of serine biosynthesis (PPSB). Mutants of phosphoserine phosphatase (PSP), the enzyme that catalyses the last step of PPSB, are embryo-lethal. When they are complemented with a construct carrying PSP1 cDNA under the control of the 35S promoter (psp1.1 35S:PSP1), which is poorly expressed in anther tissues, plants display a wild-type phenotype, but are male-sterile. The pollen from the psp1.1 35S:PSP1 lines are shrunken and unviable. Here we report the morphological alterations that appear in the psp1.1 35S:PSP1 lin…
Manipulating mtDNA in vivo reprograms metabolism via novel response mechanisms.
2019
Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activ…
Changes in the proton potential and the cellular energetics of Escherichia coli during growth by aerobic and anaerobic respiration or by fermentation.
1998
The energetic parameters of Escherichia coli were analyzed for the aerobic/anaerobic transition. The electrochemical proton potential (delta p) across the cytoplasmic membrane was determined in the steady state of respiration with O2, nitrate, fumarate, dimethylsulfoxide (Me2SO), and for fermentation. With O2, a proton potential of -160 mV was obtained. For anaerobic respiration with nitrate, fumarate or Me2SO, delta p decreased only slightly by about 20 mV in contrast to earlier assumptions, whereas delta p dropped by approximately 40 mV during fermentation. Under all conditions, the membrane potential (delta psi) contributed the major portion to delta p. The cellular ATP levels were highe…