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1.
Lowe DB Shearer MH Jumper CA Kennedy RC 《Cellular and molecular life sciences : CMLS》2007,64(7-8):803-814
SV40 was discovered as a contaminate of poliovirus vaccine lots distributed to millions of individuals in the United States
between 1955 and 1963 while contaminated vaccine batches were later circulated worldwide. After SV40 was observed to cause
in vitro animal and human cell transformations and in vivo tumor formations in animals, the search for a connection between the virus and human malignancies has continued to the present
day. Different molecular methods have been used to detect SV40 gene products in a variety of human cancers, though SV40 causality
in these tumor types has yet to be established. These data, however, are not without controversial issues related to inconclusive
SV40 serological and epidemiological evidence alongside tools and methodologies that may contribute to false-positive results
in human specimens. This review will also explore how vaccination against SV40 protein products may be used to help prevent
and treat individuals with SV40-expressing cancers.
Received 19 September 2006; received after revision 8 November 2006; accepted 13 December 2006 相似文献
2.
Identification of rate-limiting steps or components of intracellular second messenger systems holds promise to effectively
interfere with these pathways under pathological conditions. The emerging literature on a recently identified family of signalling
regulator proteins, called tribbles gives interesting clues for how these proteins seem to link several ‘independent’ signal
processing systems together. Via their unique way of action, tribbles co-ordinate the activation and suppression of the various
interacting signalling pathways and therefore appear to be key in determining cell fate while responding to environmental
challenges. This review summarises our current understanding of tribbles function and also provides an evolutionary perspective
on the various tribbles genes.
Received 10 January 2006; received after revision 20 March 2006; accepted 5 April 2006 相似文献
3.
BH3-only proteins in tumorigenesis and malignant melanoma 总被引:2,自引:0,他引:2
BH3-only proteins are a subset of the Bcl-2 family of apoptotic regulators. BH3-only proteins function as ‘damage sensors’
in the cell; they are activated in response to cellular stress or DNA damage, whereupon they initiate apoptosis. Apoptosis
is the primary mechanism by which the body rids itself of genetically defective cells and is critical for preventing the accumulation
of cells with tumorigenic potential. Therefore, dysregulation of BH3-only proteins may promote tumorigenesis. Furthermore,
functional apoptosis pathways are required for the success of most cancer treatments, including chemotherapy. Resistance to
chemotherapy, as seen with malignant melanoma, often reflects an inability of tumor cells to undergo apoptosis. By deciphering
the roles of BH3-only proteins in tumorigenesis, we may learn how to manipulate cell death pathways to overcome apoptotic
resistance. This review summarizes the current knowledge of BH3-only proteins and how they contribute to tumorigenesis, with
particular attention given to studies involving melanoma.
Received: 12 August 2006; received after revision: 2 October 2006; accepted 13 November 2006 相似文献
4.
Ribosome-inactivating proteins: progress and problems 总被引:11,自引:0,他引:11
Ribosome-inactivating proteins (RIPs), mostly from plants, are enzymes which depurinate rRNA, thus inhibiting protein synthesis.
They also depurinate other polynucleotide substrates. The biological activity of RIPs is not completely clarified, and sometimes
independent of the inhibition of protein synthesis. There are differences in the cytotoxicity of RIPs and, consequently, in
their toxicity to animals. Some RIPs are potent toxins, the best known being ricin, a potential biological weapon. New toxins
have recently been identified. RIPs cause apoptotic and necrotic lesions, and induce production of cytokines causing inflammation.
RIPs are potentially useful in agriculture and medicine because (i) they have antiviral activity and (ii) they are used for
the preparation of conjugates with antibodies (‘immunotoxins’) or other carriers, rendering them specifically toxic to the
cell target of the carrier, which may be helpful in therapy. The distribution, mechanism of action and role in nature of RIPs
are not completely understood, and we can expect several future developments in their practical application.
Received 17 February 2006; received after revision 23 March 2006; accepted 2 May 2006 相似文献
5.
Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications 总被引:30,自引:0,他引:30
Polyamines are aliphatic cations with multiple functions and are essential for life. Cellular polyamine levels are regulated by multiple pathways such as synthesis from amino acid precursors, cellular uptake mechanisms that salvage polyamines from diet and intestinal microorganisms, as well as stepwise degradation and efflux. Investigations using polyamine biosynthetic inhibitors indicate that alterations in cellular polyamine levels modulate normal and cancer cell growth. Studies using transgenic mice overexpressing polyamine biosynthetic enzymes support a role of polyamines in carcinogenesis. Many, if not all, signal transduction pathways intersect with polyamine biosynthetic pathways and the regulation of intracellular polyamine levels. Direct binding of polyamines to DNA and their ability to modulate DNA-protein interactions appear to be important in the molecular mechanisms of polyamine action in cell proliferation. Consistent with the role of polyamines as facilitators of cell growth, several studies have shown their ability to protect cells from apoptosis. However, polyamines also have a role in facilitating cell death. The basis of these diverse cellular responses is currently not known. Cell death response might be partly mediated by the production of hydrogen peroxide during polyamine catabolism. In addition, the ability of polyamines to alter DNA-protein and protein-protein interactions might be disruptive to cellular functions, when abnormally high levels are accumulated due to defects in polyamine catabolic or efflux pathways. A large body of data indicates that polyamine pathway can be a molecular target for therapeutic intervention in several types cancers. Inhibitors of biosynthesis, polyamine analogues as well as oligonucleotide/polyamine analogue combinations are promising drug candidates for chemoprevention and/or treatment of cancer. 相似文献
6.
Del Val M Iborra S Ramos M Lázaro S 《Cellular and molecular life sciences : CMLS》2011,68(9):1543-1552
CD8+ T lymphocytes screen the surface of all cells in the body to detect pathogen infection or oncogenic transformation. They
recognize peptides derived from cellular proteins displayed at the plasma membrane by major histocompatibility complex (MHC)
class I molecules. Peptides are mostly by-products of cytosolic proteolytic enzymes. Peptidic ligands of MHC class I molecules
are also generated in the secretory and vesicular pathways. Features of protein substrates, of proteases and of available
MHC class I molecules for loading peptides in these compartments shape a singular collection of ligands that also contain
different, longer, and lower affinity peptides than ligands produced in the cytosol. Especially in individuals who lack the
transporters associated with antigen processing, TAP, and in infected and tumor cells where TAP is blocked, which thus have
no supply of peptides derived from the cytosol, MHC class I ligands generated in the secretory and vesicular pathways contribute
to shaping the CD8+ T lymphocyte response. 相似文献
7.
Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of
the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan
and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes
that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties
and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of
the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition
of peptidoglycan and activation of innate immunity in insects.
Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007 相似文献
8.
The stress-activated protein kinase pathways 总被引:29,自引:0,他引:29
9.
A comparison of the frequencies of chromosomal aberrations and the rates of SV40 transformation was made using fibroblasts obtained from 2 patients with Bloom's syndrome (BS) and from a normal individual. BS cells were found to be more susceptible to chromosome damage, in confirmation of earlier reports, but surprisingly, BS cells were distinctly less prone to transformation. 相似文献
10.
Syncytin is involved in breast cancer-endothelial cell fusions 总被引:2,自引:0,他引:2
Bjerregaard B Holck S Christensen IJ Larsson LI 《Cellular and molecular life sciences : CMLS》2006,63(16):1906-1911
Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate
the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell
lines and 63 out of 165 (38%) breast cancer specimens express syncytin, an endogenous retroviral envelope protein, previously
implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express
ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression and inhibits fusions between breast
cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial
cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial
cell fusions.
Received 2 May 2006; received after revision 7 June 2006; accepted 12 June 2006 相似文献
11.
12.
13.
Calorie restriction and the nutrient sensing signaling pathways 总被引:3,自引:0,他引:3
Calorie restriction (CR) is the most potent regimen known to extend the life span in multiple species. CR has also been shown
to ameliorate several age-associated disorders in mammals and perhaps humans. CR induces diverse metabolic changes in organisms,
and it is currently unclear whether and how these metabolic changes lead to life span extension. Recent studies in model systems
have provided insight into the molecular mechanisms by which CR extends life span. In this review, we summarize and provide
recent updates on multiple nutrient signaling pathways that have been connected to CR and longevity regulation. The roles
of highly conserved longevity regulators – the Sirtuin family – in CR are also discussed.
Received 25 August 2006; received after revision 9 October 2006; accepted 13 December 2006 相似文献
14.
Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways 总被引:1,自引:0,他引:1
M. Y. Lee S. H. Lee J. H. Park H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(8):1467-1478
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal,
although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [3H]-thymidine incorporation as well as cyclin expression and decreased p27kip1 expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2.
In addition, inhibition of caveolin-1 by small interfering RNA and methyl-β-cyclodextrin (Mβ-CD) decreased galectin-1-induced
cyclin expression and [3H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced
phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mβ-CD. Furthermore, mTOR phosphorylation was
decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27kip1 was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src,
caveolin-1 Akt, and mTOR signaling pathways.
Received 30 October 2008; received after revision 18 February 2009; accepted 24 February 2009 相似文献
15.
Yeung TM Chia LA Kosinski CM Kuo CJ 《Cellular and molecular life sciences : CMLS》2011,68(15):2513-2523
The gastrointestinal epithelium is a highly organised tissue that is constantly being renewed. In order to maintain homeostasis,
the balance between intestinal stem cell (ISC) self-renewal and differentiation must be carefully regulated. In this review,
we describe how the intestinal stem cell niche provides a unique environment to regulate self-renewal and differentiation
of ISCs. It has traditionally been believed that the mesenchymal myofibroblasts play an important role in the crosstalk between
ISCs and the niche. However, recent evidence in Drosophila and in vertebrates suggests that epithelial cells also contribute to the niche. We discuss the multiple signalling pathways
that are utilised to regulate stemness within the niche, including members of the Wnt, BMP and Hedgehog pathways, and how
aberrations in these signals lead to disruption of the normal crypt–villus axis. Finally, we also discuss how CDX1 and inhibition
of the Notch pathway are important in specifying enterocyte and goblet cell differentiation respectively. 相似文献
16.
The mitogen-activated protein kinase (MAPK) pathways are known to be involved in various processes of growth, differentiation
and cell death. In spite of their ubiquitous presence and seemingly enormous cross-talk with each other, their action is very
specific. This review deals with various aspects of the three different MAPK pathways (ERK, p38 and JNK) and how their specificity
is brought about.
Received 1 April 2008; received after revision 18 June 2008; accepted 18 June 2008 相似文献
17.
18.
Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies 总被引:3,自引:0,他引:3
Borrell-Pagès M Zala D Humbert S Saudou F 《Cellular and molecular life sciences : CMLS》2006,63(22):2642-2660
Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary
movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains
a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin.
Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational
modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the
brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood
but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses
on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to
new therapeutic approaches.
Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006 相似文献
19.
On the basis of evidence collected from the literature, we propose a general model by which protein kinase (PK) A and the
different PKC isoforms can inversely affect cell growth. Molecular switches, which are able to direct the signal towards antiproliferative
or mitogenic pathways, are the different isoforms of Raf and PKC. Conflicting data are also reported and discussed in an attempt
to reconcile them.
Received 10 November 2005; received after revision 28 December 2005; accepted 3 January 2006 相似文献
20.
L. Fesus A. Madi Z. Balajthy Z. Nemes Z. Szondy 《Cellular and molecular life sciences : CMLS》1996,52(10-11):942-949
Clarification of the molecular details of forms of natural cell death, including apoptosis, has become one of the most challenging issues of contemporary biomedical sciences. One of the effector elements of various cell death pathways is the covalent cross-linking of cellular proteins by transglutaminases. This review will discuss the accumulating data related to the induction and regulation of these enzymes, particularly of tissue type transglutaminase, in the molecular program of cell death. A wide range of signalling pathways can lead to the parallel induction of apoptosis and transglutaminase, providing a handle for better understanding the exact molecular interactions responsible for the mechanism of regulated cell death. 相似文献