Search results for "Enzyme complex"
showing 10 items of 55 documents
Antigen-processing machinery breakdown and tumor growth.
2000
Defects in the major histocompatibility complex (MHC) class I antigen-processing machinery (APM) have been described in tumors of different histology. Murine data suggest that defects in the MHC class II APM might also be associated with malignant transformation of human cells. This article describes the pathophysiology of the MHC class I and II APM, reviews APM abnormalities in tumor cells and discusses their role in the escape of tumor cells from in vitro recognition by T cells.
Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I.
2000
Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the Annonaceae family. Some of them are promising candidates to be a future new generation of antitumor drugs due to the ability to inhibit the NADH:ubiquinone oxidoreductase of the respiratory chain (mitochondrial complex I), main gate of the energy production in the cell. ACG are currently being tested on standard antitumor trials although little is known about the structure activity relationship at the molecular level. On recent studies, the relevance of several parts of the molecule for the inhibitory potency has been evaluated. Due to the great diversity of skeletons included in this family of…
Gene amplification in fibroblasts from ataxia telangiectasia (AT) patients and in X-ray hypersensitive AT-like Chinese hamster mutants.
2001
In search of functions involved in the regulation of gene amplification, and given the relevance of chromosome breakage in initiating the process, we analyzed the gene amplification ability of cells hypersensitive to inducers of DNA double-strand breaks and defective in cell cycle control: two human fibroblast strains derived from patients affected by ataxia telangiectasia (AT) and two hamster mutant cell lines belonging to complementation group XRCC8 of the rodent X-ray-sensitive mutants. These mutants are considered hamster models of AT cells. To measure gene amplification, the frequency and the rate of occurrence of N-(phosphonacetyl)-L-aspartate resistant cells were determined. In both …
Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expre…
1998
The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post-implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)-gamma or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP-2 and LMP-7 and the peptide transporters TAP-1 and TAP-2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN-gamma regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human …
AICA-ribosiduria due to ATIC deficiency: Delineation of the phenotype with three novel cases, and long-term update on the first case.
2020
5-Amino-4-imidazolecarboxamide-ribosiduria (AICA)-ribosiduria is an exceedingly rare autosomal recessive condition resulting from the disruption of the bifunctional purine biosynthesis protein PURH (ATIC), which catalyzes the last two steps of de novo purine synthesis. It is characterized biochemically by the accumulation of AICA-riboside in urine. AICA-ribosiduria had been reported in only one individual, 15 years ago. In this article, we report three novel cases of AICA-ribosiduria from two independent families, with two novel pathogenic variants in ATIC. We also provide a clinical update on the first patient. Based on the phenotypic features shared by these four patients, we define AICA-…
Inhibitory effects on mitochondrial complex I of semisynthetic mono-Tetrahydrofuran acetogenin derivatives
2003
Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety or in the alkyl chain that links this terminal gamma-lactone with the alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.
Preferential induction of 20S proteasome subunits during elicitation of plant defense reactions: towards the characterization of "plant defense prote…
2003
Plants have evolved efficient mechanisms to resist pathogens. The earliest defense response is the hypersensitive response (HR) considered as the main step leading to plant systemic acquired resistance (SAR) that protects the whole plant against a large spectrum of pathogens. We showed previously that elicitation of defense reactions in tobacco cells by cryptogein, a proteinaceous elicitor of plant defense reactions, leads to a rapid and differential accumulation of transcripts corresponding to genes encoding defense-induced (din) subunits of 20S proteasome: beta1din, alpha3din and alpha6din.Here, expression of these three subunits was investigated by Northern blotting and by Western blotti…
Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells.
2000
Proteolysis mediated by the ubiquitin-proteasome system has been implicated in the regulation of programmed cell death. Here we investigated the differential effects of proteasomal inhibitors on the viability of proliferating and quiescent primary endothelial cells in vitro and in vivo. Subconfluent, proliferating cells underwent carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI) -induced apoptosis at low concentrations (EC(50)=24 nM), whereas at least 340-fold higher concentrations of PSI were necessary to obtain the same effect in confluent, contact-inhibited cells. PSI-mediated cell death could be blocked by a caspase-3 inhibitor (Ac-DEVD-H), but not by a caspase…
Cryptogein affects expression of alpha3, alpha6 and beta1 20S proteasome subunits encoding genes in tobacco.
2001
Twelve a and b 20S proteasome subunits cDNAs showing 70–82% identity with the corresponding genes in Arabidopsis or rice, and features of eukaryotic proteasome subunits were cloned in tobacco. Only b1-tcI 7, a3 and a6, 20S proteasome subunits encoding genes were up-regulated by cryptogein, a proteinaceous elicitor of plant defence reactions. These results led to the hypothesis that the activation of b1-tcI 7, a3 and a6 could induce a specific proteolysis involved in the hypersensitive response and systemic acquired resistance monitored by cryptogein. In eukaryotes, the 26S proteasome is the central multicatalytic proteinase complex comprising two subcomplexes: the 20S core particle that per…
High frequency of functionally active Melan-a-specific T cells in a patient with progressive immunoproteasome-deficient melanoma.
2004
AbstractTumor-reactive T cells play an important role in cancer immunosurveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A–specific CTLs in a melanoma patient with progressive lymph node metastases, consisting of 18 and 12.8% of total peripheral blood and tumor-infiltrating CD8+ T cells, respectively. Melan-A–specific CTLs revealed a high cytolytic activity against allogeneic Melan-A–expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I antigen processing and presentation pathway. Mutations of t…