Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism. © 2001 Cancer Research Campaign http://www.bjcancer.co

Uncovering Ubiquitin and Ubiquitin-like Signaling Networks

Microscopic imaging and technolog

Annexe III - Bibliographies

Galisson Robert, Schmitt R. Annexe III - Bibliographies . In: Repères pour la rénovation de l'enseignement du français à l'école élémentaire, n°7, 1971. Stage sur l'enseignement du vocabulaire (I.P.N. 25-28 février 1970) sous la direction de H. Romian et J. Dornel. pp. 97-99

Annexe III - Bibliographies

Galisson Robert, Schmitt R. Annexe III - Bibliographies . In: Repères pour la rénovation de l'enseignement du français à l'école élémentaire, n°7, 1971. Stage sur l'enseignement du vocabulaire (I.P.N. 25-28 février 1970) sous la direction de H. Romian et J. Dornel. pp. 97-99

Campagne Mesopac: Leve de sites de forages ODP en sismique multitraces dans le bassin de Nauru

The Mesopac Cruise was the first multichannel seismic study of the western basins of the Pacific Plate. It was concentrated in the Nauru Basin and in the western area of the Central Pacific Basin. Profiles were calibrated with drilling results from DSDP Sites 462 and 169. For the first time one could observe reflectors within the Cretaceous volcanic complex down to approximately equals 8.5 seconds. Profiles did not allow direct observation of the top of the oceanic crust. After correcting for the load on top of the oceanic crust, results suggest that it cannot lie much deeper than those reflectors. If the oceanic crust lies only a few hundred meters beneath the 2.4 km thick complex, it would be right on the normal thermal subsidence curve corresponding to a Jurassic age

The Candida glabrata glycogen branching enzyme structure reveals unique features of branching enzymes of the Saccharomycetaceae phylum

International audienceAbstract Branching enzymes (BE) are responsible for the formation of branching points at the 1,6 position in glycogen and starch, by catalyzing the cleavage of α-1,4-linkages and the subsequent transfer by introducing α-1,6-linked glucose branched points. BEs are found in the large GH13 family, eukaryotic BEs being mainly classified in the GH13_8 subfamily, GH13_9 grouping almost exclusively prokaryotic enzymes. With the aim of contributing to the understanding of the mode of recognition and action of the enzymes belonging to GH13_8, and to the understanding of features distinguishing these enzymes from those belonging to subfamily 13_9 we solved the crystal structure of the glycogen branching enzyme (GBE) from the yeast Candida glabrata, CgGBE, in ligand free forms and in complex with a maltotriose. The structures revealed the presence of a domain already observed in Homo sapiens and Oryza sativa BEs and that we named α-helical N-terminal domain, in addition to the three conserved domains found in BE. We confirmed by phylogenetic analysis that this α-helical N-terminal domain is always present in the GH13_8 enzymes suggesting that it could actually present a signature for this subfamily. We identified two binding sites (BS) in the α-helical N-terminal domain and in the carbohydrate binding module 48 (CBM48), respectively, which show a unique structural organization only present in the Saccharomycotina phylum. Our structural and phylogenetic investigation provides new insight into the structural characterization of GH13_8 GBE revealing unique structural features only present in the Saccharomycotina phylum thereby conferring original properties to this group of enzymes

Tertiary and Quaternary Structure Organization in GMP Synthetases: Implications for Catalysis

International audienceGlutamine amidotransferases, enzymes that transfer nitrogen from Gln to various cellular metabolites, are modular, with the amidotransferase (GATase) domain hydrolyzing Gln, generating ammonia and the acceptor domain catalyzing the addition of nitrogen onto its cognate substrate. GMP synthetase (GMPS), an enzyme in the de novo purine nucleotide biosynthetic pathway, is a glutamine amidotransferase that catalyzes the synthesis of GMP from XMP. The reaction involves activation of XMP though adenylation by ATP in the ATP pyrophosphatase (ATPPase) active site, followed by channeling and attack of NH3 generated in the GATase pocket. This complex chemistry entails co-ordination of activity across the active sites, allosteric activation of the GATase domain to modulate Gln hydrolysis and channeling of ammonia from the GATase to the acceptor active site. Functional GMPS dimers associate through the dimerization domain. The crystal structure of the Gln-bound complex of Plasmodium falciparum GMPS (PfGMPS) for the first time revealed large-scale domain rotation to be associated with catalysis and leading to the juxtaposition of two otherwise spatially distal cysteinyl (C113/C337) residues. In this manuscript, we report on an unusual structural variation in the crystal structure of the C89A/C113A PfGMPS double mutant, wherein a larger degree of domain rotation has led to the dissociation of the dimeric structure. Furthermore, we report a hitherto overlooked signature motif tightly related to catalysis