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

The function of P-selectin glycoprotein ligand-1 is conserved from ancestral fishes to mammals.

PSGL-1 is a mucin-like glycoprotein that supports, in mammals, leukocyte rolling on selectins. However, we have limited knowledge whether its function is conserved in non-mammals and how its structure adapted during evolution. To identify conserved amino acid sequences required for selectin binding, we performed multiple alignments of PSGL-1 sequences from 18 mammals, 4 birds, 3 reptiles, 1 amphibian, and 15 fishes. The amino-terminal T[D/E]PP[D/E] motif, which identifies in mammals a core-2 O-glycosylated threonine required for selectin-binding, is partially conserved in some fishes (e.g., T. rubripes) and birds (e.g., G. gallus), however, most non-mammals do not display it. The sulfated tyrosine residues of human PSGL-1, which bind L- and P-selectin, are not observed in non-mammals, suggesting that they are dispensable for selectin-binding or that other amino acids play their role. A mucin-like domain is present in all species. Interestingly, the alignment of cytoplasmic sequences of non-mammals reveals the conservation of ezrin/radixin/moesin binding site and two new motifs (M1 and M2). To examine the conservation of PSGL-1 function, we cloned PSGL-1 cDNA sequences of zebrafish and fugu, and established their cross-reactivity with human selectins under flow conditions. Importantly, deleting the well-conserved M1 motif strongly decreased PSGL-1 expression at leukocyte surface and induced retention of the precursor molecule in the endoplasmic reticulum, indicating that M1 motif provides a signal required to export PSGL-1 precursors to the Golgi complex. These data show for the first time the conservation of PSGL-1 function from fishes to mammals and reveal the function of a new motif

Interaction of Penicillin-Binding Protein 2x and Ser/Thr protein kinase StkP, two key players in Streptococcus pneumoniae R6 morphogenesis

International audienceBacterial cell growth and division require the co-ordinated action of peptidoglycan biosynthetic enzymes and cell morphogenesis proteins. However, the regulatory mechanisms that allow generating proper bacterial shape and thus preserving cell integrity remain largely uncharacterized, especially in ovococci. Recently, the conserved eukaryotic-like Ser/Thr protein kinase of Streptococcus pneumoniae (StkP) was demonstrated to play a major role in cell shape and division. Here, we investigate the molecular mechanisms underlying the regulatory function(s) of StkP and show that it involves one of the essential actors of septal peptidoglycan synthesis, Penicillin-Binding Protein 2x (PBP2x). We demonstrate that StkP and PBP2x interact directly and are present in the same membrane-associated complex in S. pneumoniae. We further show that they both display a late-division localization pattern at the division site and that the positioning of PBP2x depends on the presence of the extracellular PASTA domains of StkP. We demonstrate that StkP and PBP2x interaction is mediated by their extracellular regions and that the complex formation is inhibited in vitro in the presence of cell wall fragments. These data suggest that the role of StkP in cell division is modulated by an interaction with PBP2x