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1.
Thrombospondins: from structure to therapeutics 总被引:2,自引:0,他引:2
The thrombospondins (TSPs) are a family of five proteins that are involved in the tissue remodeling that is associated with embryonic development, wound healing, synaptogenesis, and neoplasia. These proteins mediate the interaction of normal and neoplastic cells with the extracellular matrix and surrounding tissue. In the tumor microenvironment, TSP-1 has been shown to suppress tumor growth by inhibiting angiogenesis and by activating transforming growth factor beta. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival, and through effects on vascular endothelial cell growth factor bioavailability. In addition, TSP-1 may affect tumor cell function through interaction with cell surface receptors and regulation of extracellular proteases. Whereas the role of TSP-1 in the tumor microenvironment is the best characterized, the other TSPs may have similar functions. (Part of a Multi-author Review). 相似文献
2.
Studies in the past years have implicated multispan transmembrane transport molecules of the ATP binding cassette (ABC) transporter
family in cellular lipid export processes. The prototypic ABC transporter ABCA1 has recently been demonstrated to act as a
major facilitator of cellular cholesterol and phospholipid export. Moreover, the transporter ABCA4 (ABCR) plays a pivotal
role in retinaldehyde processing, and ABCA3 has recently implicated in lung surfactant processing. These pioneering observations
have directed considerable attention to the A subfamily of ABC proteins. ABCA2 is the codefining member of the ABC A-transporter
subclass. Although known for some time, it was not until recently that its complete molecular structure was established. Unlike
other ABC A-subfamily members, ABCA2 is predominantly expressed in the brain and neural tissues. The unique expression profile
together with available structural data suggest roles for this largest known ABC protein in neural transmembrane lipid export.
Received 31 January 2002; received after revision 11 March 2002; accepted 11 March 2002 相似文献
3.
Roberts DD 《Cellular and molecular life sciences : CMLS》2008,65(5):667-671
Thrombospondins are large secreted, multimodular, calcium-binding glycoproteins that have complex roles in mediating cellular
processes. Determination of high-resolution structures of thrombospondins has revealed unique and interesting protein motifs.
Here, we review this progress and discuss implications for function. By combining structures of modules from thrombospondins
and related extracellular proteins it is now possible to prepare an overall model of the structure of thrombospondin-1 and
thrombospondin-2 and discern features of other thrombospondins. (Part of a multi-author Review) 相似文献
4.
Thrombospondins are large secreted, multimodular, calcium-binding glycoproteins that have complex roles in mediating cellular
processes. Determination of high-resolution structures of thrombospondins has revealed unique and interesting protein motifs.
Here, we review this progress and discuss implications for function. By combining structures of modules from thrombospondins
and related extracellular proteins it is now possible to prepare an overall model of the structure of thrombospondin-1 and
thrombospondin-2 and discern features of other thrombospondins. (Part of a multi-author Review) 相似文献
5.
Annexins: what are they good for? 总被引:2,自引:0,他引:2
J. Mollenhauer 《Cellular and molecular life sciences : CMLS》1997,53(6):506-507
Annexins comprise a unique family of calcium- and phospholipid-binding proteins. At least one of the twenty members thus
far described from this family can be found expressed in nearly every eukaryotic cell type. As common as these proteins may
be, no one clear function for all has been established. Historically, individual members of this family have been given various
names describing their ability to associate with a host of intra- and extracellular proteins and with cellular lipid membranes.
The collection of reviews in this issue of CMLS represents an effort to offer a coordinated view of the research activities
in the field and to extract structural and functional commonalities. 相似文献
6.
D.B. Moody 《Cellular and molecular life sciences : CMLS》2001,58(10):1461-1474
T cells are well known to recognize peptide antigens presented by major histocompatibility (MHC) class I or class II molecules.
More recently, the CD1 family of antigen-presenting molecules has been shown to present both mammalian and microbial glycolipid
antigens for specific recognition by T cells. Human CD1c proteins mediate T cell recognition of polyisoprenyl glycolipids,
evolutionarily conserved phosphoglycolipids, which function in glycan synthesis pathways. This family of antigenic molecules
is particularly attractive for the study of the molecular features that control T cell recognition of self and foreign glycolipids
because natural polyisoprenols from mammals, fungi, protozoa, mycobacteria and eubacteria differ in structure. Moreover, these
naturally occurring structural differences can influence their recognition by CD1c-restricted T cells. This review of the
structural diversity and evolutionary relationships of polyisoprenoid glycolipids emphasizes those features of polyisoprenyl
glycolipid biosynthesis that are relevant to their functions as targets of CD1-mediated T cell responses.
Received 16 March 2001; received after revision 19 April 2001; accepted 23 April 2001 相似文献
7.
Amelogenin gene splice products: potential signaling molecules 总被引:3,自引:0,他引:3
Veis A 《Cellular and molecular life sciences : CMLS》2003,60(1):38-55
The amelogenins, the major proteins of the developing tooth enamel matrix, are highly conserved throughout most species studied.
The gene structure is similar, with a set of seven exons and intervening introns, and remarkable conservation of particular
exon sizes over divergent species. Studies of exon skipping and consequent alternative gene splicing suggest that, in vertebrates,
exon definition is crucial. In this mechanism, exon size is important. If too small, an exon can be readily skipped, if too
large, internal cryptic splice sites may be utilized. Other factors, such as intron length and specific nucleotide sequences
at the splice boundaries also modulate splicing efficiency, but amelogenin gene splicing conforms well to the generalized
exon length model. Exons 1, 2 and 7 are not subject to splicing that affects the secreted protein product, but exons 3, 4
and 5 are at the lower boundary of exon size, rendering them, 4 and 5 especially, subject to skipping. On the other hand,
exon 6 is very long and has cryptic splicing sites that can be used. In the mouse, nine distinct splice product proteins have
been detected. The question now is the functions of these products. The larger forms, those that contain the intact proline-rich,
hydrophobic exon 6 domains, are important for enamel mineralization. Recent work suggests that the small proteins resulting
from deletion of a major part of amelogenin gene exon 6 via utilization of a cryptic site may have signal transduction
functions during tooth development. Furthermore, new work also suggests that odontoblasts transiently express the small amelogenins
during the period that epithelial-mesenchymal signaling between preodontoblasts and preameloblasts determines the course of
tooth development. The same peptides have been demonstrated to act on non-odontogenic cells and effect their phenotypic expression
patterns in vitro, and to induce bone formation in implants in vivo.
Received 20 March 2002; received after revision 2 July 2002; accepted 3 July 2002 相似文献
8.
Ras proteins in the control of the cell cycle and cell differentiation 总被引:12,自引:0,他引:12
The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in
the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream
through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. While constitutive
Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate
cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15INK4b, p16INK4a, p19ARF, and p21WAF1 accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied
so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly
muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation,
in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects of Ras in animal cells
are discussed.
Received 8 March 2000; received after revision 24 May 2000; accepted 24 May 2000 相似文献
9.
Functions and malfunctions of the tau proteins 总被引:9,自引:1,他引:8
The tau proteins belong to the family of microtubule-associated proteins. They are mainly expressed in neurons where they
play major regulatory roles in the organization and integrity of the cytoskeleton network. Neurofibrillary changes of abnormally
hyperphosphorylated tau are a key lesion in Alzheimer's disease and a number of other tauopathies. However, despite an ever-increasing
body of data on the changes which tau undergoes in disease, its role regarding the fundamental disease process is still unclear.
Moreover, conceptions of tau functions continue to evolve, which complicates an understanding of its role in the disease process.
This review attempts to summarize data on the role of tau proteins in the context of both normal cellular function and dysfunction.
Furthermore, we try to develop a mechanistic framework for the involvement of tau during the disease process. The review closes
with a look towards various approaches to elucidate the functions and malfunctions of tau.
Received 21 June 2002; received after revision 24 July 2002; accepted 29 July 2002
RID="*"
ID="*"Corresponding author. 相似文献
10.
Noncollagenous, nonproteoglycan macromolecules of cartilage 总被引:4,自引:0,他引:4
Extracellular matrix comprises approximately 90% of cartilage, with collagens and proteoglycans making up the bulk of the
tissue. In recent years, several abundant cartilage proteins that are neither collagens nor proteoglycans have been characterized
in detail. The putative roles of these proteins range from involvement in matrix organization or matrix-cell signaling (PRELP,
chondroadherin, cartilage oligomeric protein and cartilage matrix protein) through to molecules that are likely to be involved
with modulation of the chondrocyte phenotype (CD-RAP, CDMPs, chondromodulin and pleiotrophin). Other molecules, such as the
cartilage-derived C-type lectin and cartilage intermediate layer protein have no role as yet. Due to the difficulties associated
with experimentally manipulating a tissue that is 90% extracellular matrix in a manner that can be readily transferred to
the whole organism, many of these molecules have been focused on by a surprisingly small number of researchers. This review
focuses on newly discovered proteins and glycoproteins in cartilage, with a bias towards those that have structural roles
or that are unique to cartilage.
Received 7 January 1999; accepted 11 March 1999 相似文献
11.
12.
Davoli C Marconi A Serafino A Iannoni C Marcheggiano A Ravagnan G 《Cellular and molecular life sciences : CMLS》2002,59(3):527-539
Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a family of proteins binding the same p75 receptor
and closely related members of the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate nervous system,
neurotrophin signals have also been suggested as essential for relatively complex nervous systems occurring in invertebrate
species that live longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian neurotrophins have been found to influence invertebrate neuronal growth. However, there are only a few data on
the presence of molecules related to neurotrophin signalling components in invertebrates. Our studies provide evidence that
analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins are both expressed in the nervous system, whereas
p75-like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response
to mechanical irritation or stress.
Received 12 November 2001; received after revision 8 January 2002; accepted 8 January 2002 相似文献
13.
Viviani VR 《Cellular and molecular life sciences : CMLS》2002,59(11):1833-1850
Luciferases are the enzymes that catalyze the reactions that produce light in bioluminescence. Whereas the oxidative mechanism
which leads to light emission is similar for most luciferases, these enzymes and their substrates are evolutionarily unrelated.
Among all bioluminescent groups, insects constitute one of the most diverse in terms of biochemistry. In the fungus-gnats
(Mycetophilidae: Diptera), for example, bioluminescence is generated by two biochemically distinct systems. Despite the diversity,
investigations on insect luciferases and biochemistry have been conducted mostly with fireflies. The luciferases from the
related phengodid beetles, which can produce green to red bioluminescence using the same chemistry as firefly luciferases,
have been recently investigated. Beetle luciferases originated from ancestral acyl-CoA ligases. Present data suggest that
conserved motifs among this class of ligases are involved in substrate adenylation. The three-dimensional structure of firefly
luciferase was recently solved and mutagenesis studies have been performed identifying putative residues involved in luciferin
binding and bioluminescence color determination in several beetle luciferases. The knowledge gained through these studies
is helping in the development of useful reporter gene tools for biotechnological and biomedical purposes.
Received 4 March 2002; received after revision 13 May 2002; accepted 21 May 2002 相似文献
14.
Di Francesco AM Ruggiero A Riccardi R 《Cellular and molecular life sciences : CMLS》2002,59(11):1914-1927
Oxaliplatin (Eloxatine) is a third-generation platinum compound which has shown a wide antitumour effect both in vitro and
in vivo, a better safety profile than cisplatin and a lack of cross-resistance with cisplatin and carboplatin. In this scenario,
oxaliplatin may represent an innovative and challenging drug extending the antitumour activity in diseases such as gastrointestinal
cancer that are not usually sensitive to these coordination complexes. Oxaliplatin has a non-hydrolysable diaminocyclohexane
(DACH) carrier ligand which is maintained in the final cytotoxic metabolites of the drug. Like cisplatin, oxaliplatin targets
DNA producing mainly 1,2-GG intrastrand cross-links. The cellular and molecular aspects of the mechanism of action of oxaliplatin
have not yet been fully elucidated. However, the intrinsic chemical and steric characteristics of the DACH-platinum adducts
appear to contribute to the lack of cross-resistance with cisplatin. To date, mismatch repair and replicative bypass appear
to be the processes most likely involved in differentiating the molecular responses to these agents.
Received 15 March 2002; received after revision 13 May 2002; accepted 21 May 2002
RID="*"
ID="*"Corresponding author. 相似文献
15.
Genetic and molecular analysis of the synaptotagmin family 总被引:5,自引:0,他引:5
Secretion is a fundamental cellular process used by all eukaryotes to insert proteins into the plasma membrane and transport
signaling molecules and intravesicular proteins into the extracellular space. Secretion requires the fusion of two phospholipid
bilayers within the cell, an energetically unfavorable process. A conserved repertoire of vesicle-trafficking proteins has
evolved that function to overcome this energy barrier and temporally and spatially control membrane fusion within the cell.
Within neurons, opening of synaptic calcium channels and subsequent calcium entry triggers synchronous synaptic vesicle exocytosis
and neurotransmitter release into the synaptic cleft. After fusion, synaptic vesicles undergo endocytosis, are refilled with
neurotransmitter, and return to the vesicle pool for further rounds of cycling. It is within this local synaptic trafficking
pathway that the synaptotagmin family of calcium-binding synaptic vesicle proteins has been postulated to function. Here we
review the current literature on the function of the synaptotagmin family and discuss the implications for synaptic transmission
and membrane trafficking.
Received 14 August 2000; received after revision 20 September 2000, accepted 14 October 2000 相似文献
16.
Molecular basis of autosomal-dominant polycystic kidney disease 总被引:5,自引:0,他引:5
Gallagher AR Hidaka S Gretz N Witzgall R 《Cellular and molecular life sciences : CMLS》2002,59(4):682-693
Autosomal-dominant polycystic kidney disease (ADPKD) is one of the most common monogenetic diseases in humans. The discovery
that mutations in the PKD1 and PKD2 genes are responsible for ADPKD has sparked extensive research efforts into the physiological and pathogenetic role of polycystin-1
and polycystin-2, the proteins encoded by these two genes. While polycystin-1 may mediate the contact among cells or between
cells and the extracellular matrix, a lot of evidence suggests that polycystin-2 represents an endoplasmic reticulum-bound
cation channel. Cyst development has been compared to the growth of benign tumors and this view is highlighted by the model
that a somatic mutation in addition to the germline mutation is responsible for cystogenesis (two-hit model of cyst formation).
Since in vitro polycystin-1 and polycystin-2 interact through their COOH termini, the two proteins possibly act in a common
pathway, which controls the width of renal tubules. The loss of one protein may lead to a disruption of this pathway and to
the uncontrolled expansion of tubules. Our increasing knowledge of the molecular events in ADPKD has also started to be useful
in designing novel diagnostic and therapeutic strategies.
Received 12 September 2001; received after revision 7 November 2001; accepted 7 November 2001 相似文献
17.
Johansson S Gullbo J Lindholm P Ek B Thunberg E Samuelsson G Larsson R Bohlin L Claeson P 《Cellular and molecular life sciences : CMLS》2003,60(1):165-175
Four novel proteins (phoratoxins C–F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and
trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist
of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins
A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several
cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic
phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast
cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.
Received 30 September 2002; received after revision 28 October 2002; accepted 7 November 2002
RID="*"
ID="*"Corresponding author. 相似文献
18.
M. Mrksich 《Cellular and molecular life sciences : CMLS》1998,54(7):653-662
Substrates for studies of the interactions of attached cells with extracellular matrix components are often prepared by allowing
a protein to adsorb from solution onto a glass or polystyrene substrate. This method is simple and effective for many studies,
but it can fail in cases that require rigorous control over the structure and composition of adsorbed protein. Self-assembled
monolayers formed by the spontaneous ordering of terminally functionalized alkanethiols onto a gold substrate are a class
of well-ordered substrates and provide a convenient method for tailoring substrates with ligands, proteins and other groups.
Methods that can pattern the monolayers provide a general strategy to create substrates that control the size, shape and spacing
of attached cells. This review illustrates recent work that has used these methods of surface chemistry to create tailored
substrates for studies in cell biology.
Received 14 November 1997; received after revision 10 March 1998; accepted 10 March 1998 相似文献
19.
Recognition of bacterial peptidoglycan by the innate immune system 总被引:15,自引:0,他引:15
Dziarski R 《Cellular and molecular life sciences : CMLS》2003,60(9):1793-1804
The innate immune system recognizes microorganisms through a series of pattern recognition receptors that are highly conserved in evolution. Peptidoglycan (PGN) is a unique and essential component of the cell wall of virtually all bacteria and is not present in eukaryotes, and thus is an excellent target for the innate immune system. Indeed, higher eukaryotes, including mammals, have several PGN recognition molecules, including CD14, Toll-like receptor 2, a family of peptidoglycan recognition proteins, Nod1 and Nod2, and PGN-lytic enzymes (lysozyme and amidases). These molecules induce host responses to microorganisms or have direct antimicrobial effects.Received 15 January 2003; received after revision 28 February 2003; accepted 26 March 2003 相似文献
20.
Specialised copper sites have been recruited during evolution to provide long-range electron transfer reactivity and oxygen
binding and activation in proteins destined to cope with oxygen reactivity in different organisms. Ceruloplasmin is an ancient
multicopper oxidase evolved to insure a safe handling of oxygen in some metabolic pathways of vertebrates. The presently available
knowledge of its structure provides a glimpse of its plasticity, revealing a multitude of binding sites that point to an elaborate
mechanism of multifunctional activity. Ceruloplasmin represents an example of a 'moonlighting' protein that overcomes the
one gene-one structure-one function concept to follow the changes of the organism in its physiological and pathological conditions.
Received 19 February 2002; received after revision 29 March 2002; accepted 2 April 2002
RID="*"
ID="*"Corresponding author. 相似文献