Search results for "Primer"
showing 10 items of 530 documents
The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway.
2013
Cutaneous melanoma is the fastest increasing cancer worldwide. Although several molecular abnormalities have been associated with melanoma progression, the underlying mechanisms are still largely unknown and few targeted therapies are under evaluation. Here we show that the HOXB7/PBX2 dimer acts as a positive transcriptional regulator of the oncogenic microRNA-221 and -222. In addition, demonstrating c-FOS as a direct target of miR-221&222, we identify a HOXB7/PBX2→miR-221&222 →c-FOS regulatory link, whereby the abrogation of functional HOXB7/PBX2 dimers leads to reduced miR-221&222 transcription and elevated c-FOS expression with consequent cell death. Taking advantage of the treatment wit…
Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes
2008
Apoptosis, or programmed cell death, regulates tissue development and homeostasis in multi-cellular organisms. Extrinsic or intrinsic death signals activate pro-apoptotic pathways, resulting in the activation of caspases and finally in cell death. An important event during apoptosis process is the permeabilization of the outer mitochondrial membrane (OMM). Integrity of the OMM is regulated by the Bcl-2 protein family, which is divided into three groups: anti-apoptotic members Bcl-2, Bcl-xL and myeloid cell leukemia-1 (Mcl-1), pro-apoptotic multidomain members Bax and Bak, and pro-apoptotic BH3-only proteins. Mitochondrial activation is regulated by selective interactions of Bcl-2 proteins v…
The interaction of recombinant subdomains of the procollagen C-proteinase with procollagen I provides a quantitative explanation for functional diffe…
2006
The procollagen C-proteinase (PCP) is a zinc peptidase of the astacin family and the metzincin superfamily. The enzyme removes the C-terminal propeptides of fibrillar procollagens and activates other matrix proteins. Besides its catalytic protease domain, the procollagen C-proteinase contains several C-terminal CUB modules (named after complement factors C1r and C1s, the sea urchin UEGF protein, and BMP-1) and EGF-like domains. The two major splice forms of the C-proteinase differ in their overall domain composition. The longer variant, termed mammalian tolloid (mTld, i.e., PCP-2), has the protease- CUB1-CUB2-EGF1-CUB3-EGF2-CUB4-CUB5 composition, whereas the shorter form termed bone morphog…
Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1
2001
Glucocorticoids inhibit the proinflammatory activities of transcription factors such as AP-1 and NF-kappa B as well as that of diverse cellular signaling molecules. One of these signaling molecules is the extracellular signal-regulated kinase (Erk-1/2) that controls the release of allergic mediators and the induction of proinflammatory cytokine gene expression in mast cells. The mechanism of inhibition of Erk-1/2 activity by glucocorticoids is unknown. Here we report a novel dual action of glucocorticoids for this inhibition. Glucocorticoids increase the expression of the MAP kinase phosphatase-1 (MKP-1) gene at the promoter level, and attenuate proteasomal degradation of MKP-1, which we re…
Cloning of Sponge (Geodia cydonium) and Tunicate (Botryllus schlosseri) Proteasome Subunit Epsilon (PRCE): Implications about the Vertebrate MHC-Enco…
1996
Proteasomes are large protein complexes that play a major role in selective degradation of intracellular proteins. Eukaryotes feature seven different alpha and beta subunits. Two of the vertebrate housekeeping beta-subunits have MHC-encoded homologues that can substitute for the housekeeping counterparts upon interferon-gamma induction. In the present study we report the cloning of invertebrate beta-subunit proteasome epsilon (PRCE), from the marine sponge Geodia cydonium and from the colonial tunicate Botryllus schlosseri. Sequence comparisons revealed that the sponge and tunicate proteins are strikingly similar to vertebrate and yeast PRCEs and their MHC-linked counterparts the PRCCs (als…
Functional deficiencies of components of the MHC class I antigen pathway in human tumors of epithelial origin
2000
An association between oncogenic transformation and repression of different components of the MHC class I antigen processing machinery (APM) have been described in murine model systems. In order to discover whether a similar correlation exists, human tumor cell lines of distinct histology with altered ras protein were analyzed for the expression of APM components utilizing RT-PCR and Western blot analyses. A heterogeneous expression pattern of MHC class I antigens, TAP peptide transporter, proteasome subunits, proteasome activator PA28 and the chaperones calnexin, calreticulin as well as tapasin was displayed by these tumor cell lines. Single or combined deficiencies in the expression and/o…
Development and characterization of mouse anti-human LMP2, LMP7, TAP1 and TAP2 monoclonal antibodies.
2008
Low molecular mass polypeptides (LMP) 2 and LMP7 and transporter associated with antigen processing (TAP) subunits TAP1 and TAP2 play a crucial role in antigen processing and cell surface expression of HLA class I molecules. Since monoclonal antibodies (mAb) to these molecules will facilitate the analysis of their expression, structure and function in normal and transformed cells, in the present study we have developed these reagents. Specifically anti-LMP2 and LMP7 mAb were generated from BALB/c mice immunized with specific peptides, and anti-TAP1 and TAP2 mAb from BALB/c mice immunized with respective recombinant proteins. mAb VF101-39F7 and VF101-39G5 were shown to be specific for LMP2, …
The membrane proximal cytokine receptor domain of the human interleukin-6 receptor is sufficient for ligand binding but not for gp130 association.
1998
Interleukin-6 (IL-6) belongs to the family of the "four-helix bundle" cytokines. The extracellular parts of their receptors consist of several Ig- and fibronectin type III-like domains. Characteristic of these receptors is a cytokine-binding module consisting of two such fibronectin domains defined by a set of four conserved cysteines and a tryptophan-serine-X-tryptophan-serine (WSXWS) sequence motif. On target cells, IL-6 binds to a specific IL-6 receptor (IL-6R), and the complex of IL-6.IL-6R associates with the signal transducing protein gp130. The IL-6R consists of three extracellular domains. The NH2-terminal Ig-like domain is not needed for ligand binding and signal initiation. Here w…
B7/CD28 costimulation of T cells induces a distinct proteome pattern.
2005
Effective immune strategies for the eradication of human tumors require a detailed understanding of the interaction of tumor cells with the immune system, which might lead to an optimization of T cell responses. To understand the impact of B7-mediated costimulation on T cell activation comprehensive proteome analysis of B7-primed T cell populations were performed. Using this approach we identified different classes of proteins in T cells whose expression is either elevated or reduced upon B7-1- or B7-2-mediated CD28 costimulation. The altered proteins include regulators of the cell cycle and cell proliferation, signal transducers, components of the antigen processing machinery, transporters…
Single tube optimisation of APOE genotyping based on melting curve analysis
2008
Objectives: To develop and validate a single-tube protocol for APOE genotyping using fluorescent probes. Design and methods: We have designed and validated a hybrid, single-tube, SimpleProbe/FRET probe protocol that takes advantage of the different probe wavelength emissions. Results: Our method offers high quality outcomes, minimum interferences between probe signals and is 100% concordant with the reference protocol. Conclusions: This method is cheaper, faster and more reliable and versatile than other alternatives proposed. © 2008 Elsevier Inc. All rights reserved.