Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.
Abnormalities of the p53 tumour suppressor gene are among the most frequent molecular events in human and animal neoplasia. Moreover, p53 is one of the most studied proteins in the whole of contemporary biology, with more than 12,500 papers so far written! In this review the choice has been deliberately made not to be fully comprehensive in the coverage of the huge p53 literature. Rather attention is focused on a small number of recent developments which are reviewed in the context of modern models of p53 function. Progress in the analysis of signalling to p53 including phosphorylation cascades, and interactions with proteins such as mdm2 and ARF are highlighted. The plethora of protein-protein interactions is discussed, as are the strategies for defining downstream targets of p53. Finally, the emerging biology of p53 homologues is considered. The need for bridging the gap between reductionist, biochemical and biophysical studies and biological and genetic analysis is emphasized. Only this will provide the needed framework for utilizing the information in clinical care.
High dimension, low sample size data are emerging in various areas of science. We find a common structure underlying many such data sets by using a non-standard type of asymptotics: the dimension tends to ∞ while the sample size is fixed. Our analysis shows a tendency for the data to lie deterministically at the vertices of a regular simplex. Essentially all the randomness in the data appears only as a random rotation of this simplex. This geometric representation is used to obtain several new statistical insights. Copyright 2005 Royal Statistical Society.
We have investigated the use of a novel technique, in situ end-labelling, as a means of the specific identification of apoptotic cells in formalin-fixed, paraffin-processed tissue sections. The technique relies on the presence of DNA strand breaks in apoptotic cells, caused by activation of endogenous nuclease activity during the process of cell death. These strands are labelled with a non-isotopic reporter molecule in the presence of a DNA polymerase, and labelled DNA is identified immunohistochemically. We show that in situ end-labelling stains cells with the morphological characteristics of apoptosis, and greatly simplifies their identification. Furthermore, in two model systems, the number of labelled cells parallels the number of cells undergoing apoptosis as measured by alternative techniques. The ability of the Klenow fragment of DNA polymerase to label apoptotic nuclei suggests that the characteristic DNA fragmentation seen during this process involves the formation of DNA breaks with a 5' overhang. In situ end-labelling will be valuable for the identification and quantitation of apoptosis in a range of normal tissues and in a variety of pathological states. However, the technique is not specific for programmed cell death, and results must be interpreted with caution and correlated with morphological criteria of apoptosis.
Septins are an evolutionarily conserved group of GTP-binding and filament-forming proteins that belong to the large superclass of P-loop GTPases. While originally discovered in yeast as cell division cycle mutants with cytokinesis defects, they are now known to have diverse cellular roles which include polarity determination, cytoskeletal reorganization, membrane dynamics, vesicle trafficking, and exocytosis. Septin proteins form homo-and heterooligomeric polymers which can assemble into higher-order filaments. They are also known to interact with components of the cytoskeleton, ie actin and tubulin. The precise role of GTP binding is not clear but a current model suggests that it is associated with conformational changes which alter binding to other proteins. There are at least 12 human septin genes, and although information on expression patterns is limited, most undergo complex alternative splicing with some degree of tissue specificity. Nevertheless, an increasing body of data implicates the septin family in the pathogenesis of diverse disease states including neoplasia, neurodegenerative conditions, and infections. Here the known biochemical properties of mammalian septins are reviewed in the light of the data from yeast and other model organisms. The data implicating septins in human disease are considered and a model linking these data is proposed. It is posited that septins can act as regulatable scaffolds where the stoichiometry of septin associations, modifications, GTP status, and the interactions with other proteins allow the regulation of key cellular processes including polarity determination. Derangements of such septin scaffolds thus explain the role of septins in disease states.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.