Search results for "DOM"
showing 10 items of 12668 documents
Hetero-oligomerization of Bacillus thuringiensis Cry1A proteins enhance binding to the ABCC2 transporter of Spodoptera exigua
2021
The ATP binding cassette (ABC) transporters are membrane proteins that can act as putative receptors for Cry proteins from Bacillus thuringiensis (Bt) in the midgut of different insects. For the beet armyworm, Spodoptera exigua, ABCC2 and ABCC3 have been found to interact with Cry1A proteins, the main insecticidal proteins used in Bt crops, as well as Bt-based pesticides. The ABCC2 has shown to have specific binding towards Cry1Ac and is involved in the toxic process of Cry1A proteins, but the role of this transporter and how it relates with the Cry1A proteins is still unknown. Here, we have characterized the interactions between the SeABCC2 and the main proteins that bind to the receptor. …
Indomethacin Disrupts Autophagic Flux by Inducing Lysosomal Dysfunction in Gastric Cancer Cells and Increases Their Sensitivity to Cytotoxic Drugs
2018
AbstractNSAIDs inhibit tumorigenesis in gastrointestinal tissues and have been proposed as coadjuvant agents to chemotherapy. The ability of cancer epithelial cells to adapt to the tumour environment and to resist cytotoxic agents seems to depend on rescue mechanisms such as autophagy. In the present study we aimed to determine whether an NSAID with sensitizing properties such as indomethacin modulates autophagy in gastric cancer epithelial cells. We observed that indomethacin causes lysosomal dysfunction in AGS cells and promotes the accumulation of autophagy substrates without altering mTOR activity. Indomethacin enhanced the inhibitory effects of the lysosomotropic agent chloroquine on l…
The Stalk Domain of NKp30 Contributes to Ligand Binding and Signaling of a Preassembled NKp30-CD3ζ Complex
2016
The natural cytotoxicity receptor (NCR) NKp30 (CD337) is a key player for NK cell immunosurveillance of infections and cancer. The molecular details of ligand recognition and its connection to CD3ζ signaling remain unsolved. Here, we show that the stalk domain (129KEHPQLGAGTVLLLR143) of NKp30 is very sensitive to sequence alterations, as mutations lead to impaired ligand binding and/or signaling capacity. Surprisingly, the stalk domains of NKp30 and NKp46, another NCR employing CD3ζ for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting, and/or ligand-induced receptor signaling. Further mutational studies, N-glycosylation mapping, and plasma …
Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling.
2018
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease-activated receptor 2 (PAR2) that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1. A po…
Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell…
2020
AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhib…
The Drosophila Hox gene Ultrabithorax acts both in muscles and motoneurons to orchestrate formation of specific neuromuscular connections
2016
Hox genes are known to specify motoneuron pools in the developing vertebrate spinal cord and to control motoneuronal targeting in several species. However, the mechanisms controlling axial diversification of muscle innervation patterns are still largely unknown. We present data showing that the Drosophila Hox gene Ultrabithorax (Ubx) acts in the late embryo to establish target specificity of ventrally projecting RP motoneurons. In abdominal segments A2 to A7, RP motoneurons innervate the ventrolateral muscles VL1-4, with VL1 and VL2 being innervated in a Wnt4-dependent manner. In Ubx mutants, these motoneurons fail to make correct contacts with muscle VL1, a phenotype partially resembling t…
Epithelium‐specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile
2019
Infection with Clostridium difficile is one of the major causes of health care acquired diarrhea and colitis. Signaling though MyD88 downstream of TLRs is critical for initiating the early protective host response in mouse models of C. difficile infection (CDI). In the intestine, MyD88 is expressed in various tissues and cell types, such as the intestinal epithelium and mononuclear phagocytes (MNP), including DC or macrophages. Using a genetic gain-of-function system, we demonstrate here that restricting functional MyD88 signaling to the intestinal epithelium, but also to MNPs is sufficient to protect mice during acute CDI by upregulation of the intestinal barrier function and recruitment o…
Single cell RNAseq provides a molecular and cellular cartography of changes to the human endometrium through the menstrual cycle
2018
In a human menstrual cycle, the endometrium undergoes remodeling, shedding, and regeneration which are driven by substantial gene expression changes in the underlying cellular hierarchy. Despite its importance in human fertility and regenerative biology, mechanistic understanding of this unique type of tissue homeostasis remains rudimentary. Here, we characterized the transcriptomic transformation of human endometrium at single cell resolution, dissecting multidimensional cellular heterogeneity of the tissue across the entire natural menstrual cycle. We analyzed 6 endometrial cell types, including a previously uncharacterized ciliated epithelial cell type, during four major phases of endome…
Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Dro…
2016
During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to i…
Neurofibromatosis type 2 tumor suppressor protein is expressed in oligodendrocytes and regulates cell proliferation and process formation.
2017
The neurofibromatosis type 2 (NF2) tumor suppressor protein Merlin functions as a negative regulator of cell growth and actin dynamics in different cell types amongst which Schwann cells have been extensively studied. In contrast, the presence and the role of Merlin in oligodendrocytes, the myelin forming cells within the CNS, have not been elucidated. In this work, we demonstrate that Merlin immunoreactivity was broadly distributed in the white matter throughout the central nervous system. Following Merlin expression during development in the cerebellum, Merlin could be detected in the cerebellar white matter tract at early postnatal stages as shown by its co-localization with Olig2-positi…