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1.
Protein-O-mannosyltransferases (Pmt proteins) catalyse the addition of mannose to serine or threonine residues of secretory proteins.
This modification was described first for yeast and later for other fungi, mammals, insects and recently also for bacteria.
O-mannosylation depends on specific isoforms of the three Pmt1, 2 and 4 subfamilies. In fungi, O-mannosylation determines the structure and integrity of cell walls, as well as cellular differentiation and virulence. O-mannosylation of specific secretory proteins of the human fungal pathogen Candida albicans and of the bacterial pathogen Mycobacterium tuberculosis contributes significantly to virulence. In mammals and insects, Pmt proteins are essential for cellular differentiation and
development, while lack of Pmt activity causes Walker-Warburg syndrome (muscular dystrophy) in humans. The susceptibility
of human cells to certain viruses may also depend on O-mannosyl chains. This review focuses on the various roles of Pmt proteins in cellular differentiation, development and virulence.
Received 6 September 2007; received after revision 3 October 2007; accepted 5 October 2007 相似文献
2.
Li R 《Cellular and molecular life sciences : CMLS》2007,64(23):3044-3058
Cytokinesis is a crucial step in cell proliferation, and remarkably, it is also an important mechanism for developmental regulation
in the generation of diverse cell types in eukaryotic organisms. Successful cytokinesis relies on the assembly and activation
of an actomyosin-based contractile ring and membrane deposition/fusion in a spatially and temporally precise manner. As such,
the molecular pathways governing cytokinesis are highly complex, involving a large number of components forming intricate
interactive networks. The complexity of this system, however, may have also provided a rich platform for evolutionary ‘tinkering’
to achieve specific morphogenetic and developmental outcomes. Furthermore, failed or altered cytokinesis appears to contribute
to the development of cancer in unexpected ways.
Received 25 June 2007; received after revision 20 July 2007; accepted 16 August 2007 相似文献
3.
Courtois G 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1123-1132
CYLD is a protein with tumor suppressor properties which was originally discovered associated with cylindromatosis, an inherited
cancer exclusively affecting the folicullo-sebaceous-apocrine unit of the epidermis. CYLD exhibits deubiquitinating activity
and acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TRAF2. Recent data suggest
that this is unlikely to be its unique function in vivo. CYLD has also been shown to control other seemingly disparate cellular processes, such as proximal T cell receptor signaling,
TrkA endocytosis and mitosis. In each case, this enzyme appears to act by regulating a specific type of polyubiquitination,
K63 polyubiquitination, that does not result in recognition and degradation of proteins by the proteasome but instead controls
their activity through diverse mechanisms.
Received 6 October 2007; received after revision 2 November 2007; accepted 23 November 2007 相似文献
4.
Rosenstiel P Jacobs G Till A Schreiber S 《Cellular and molecular life sciences : CMLS》2008,65(9):1361-1377
NOD-like receptors (NLRs) comprise a family of cytosolic proteins that have been implicated as ancient cellular sentinels
mediating protective immune responses elicited by intracellular pathogens or endogenous danger signals. Genetic variants in
NLR genes have been associated with complex chronic inflammatory barrier diseases (e.g. Crohn disease, bronchial asthma). In
this review, we focus on the molecular pathophysiology of NLRs in the context of chronic inflammatory diseases and pinpoint
recent advances in the evolutionary understanding of NLR biology. We propose that the field of NLRs may serve as a prototype
for how a comprehensive understanding of an element of the immunological barrier will eventually lead to the development of
targeted diagnostic, therapeutic and/or preventive strategies.
Received 29 October 2007; received after revision 10 December 2007; accepted 19 December 2007 相似文献
5.
Venkatesan A Nath A Ming GL Song H 《Cellular and molecular life sciences : CMLS》2007,64(16):2120-2132
New dentate granule cells are continuously generated from neural progenitor cells and integrated into the existing hippocampal
circuitry in the adult mammalian brain through an orchestrated process termed adult neurogenesis. While the exact function
remains elusive, adult neurogenesis has been suggested to play important roles in specific cognitive functions. Adult hippocampal
neurogenesis is regulated by a variety of physiological and pathological stimulations. Here we review emerging evidence showing
that HIV infection and several drugs of abuse result in molecular changes that may affect different aspects of adult hippocampal
neurogenesis. These new findings raise the possibility that cognitive dysfunction in the setting of HIV infection or drug
abuse may, in part, be related to alterations in hippocampal neurogenesis. A better understanding of how HIV and drugs of
abuse affect both molecular and cellular aspects of adult neurogenesis may lead to development of more effective therapeutic
interventions for these interlinked epidemics.
Received 6 February 2007; received after revision 26 March 2007; accepted 25 April 2007 相似文献
6.
Martínez-Salgado C Rodríguez-Peña AB López-Novoa JM 《Cellular and molecular life sciences : CMLS》2008,65(3):477-492
The mechanisms involved in the development of renal fibrosis are poorly understood. Small Ras GTPases control cell proliferation,
differentiation, cellular growth and apoptosis, with cell-specific expression in the kidney. Cytokines, high glucose medium
or advanced glycation end-products activate Ras in different renal cells. Increased Ras activation has been found in experimental
tubulointerstitial fibrosis. Transforming growth factor-β1 (TGF-β1) and Ras signalling pathways are close related: TGF-β1
overcomes Ras mitogenic effects, and Ras counteracts TGF-β signalling. However, Ras activation is also an intracellular signal
transduction point for several molecules (e.g. TGF-β1) involved in kidney damage. Ras isoforms play different roles in regulating extracellular matrix synthesis in fibroblasts
and mesangial cells. These data give evidence for a role for Ras in renal fibrosis, but no reviews are available on the role
of p21 Ras in this process. Thus, our goal is to review the role of Ras activation and signalling in renal fibrosis.
Received 7 June 2007; received after revision 17 September 2007; accepted 1 October 2007 相似文献
7.
Menkes disease is caused by mutations in the copper-transporting P1B-type ATPase ATP7A. ATP7A has a dual function: it serves to incorporate copper into copper-dependent enzymes, and it maintains
intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics
between different cellular locations depending on copper levels.The mechanism for sensing the concentration of copper, for
trafficking, as well as the details of the mechanism of copper translocation across the membrane are unknown.
Received 24 September 2007; received after revision 12 October 2007; accepted 17 October 2007 相似文献
8.
Myosin V from head to tail 总被引:1,自引:1,他引:0
Trybus KM 《Cellular and molecular life sciences : CMLS》2008,65(9):1378-1389
Myosin V (myoV), a processive cargo transporter, has arguably been the most well-studied unconventional myosin of the past
decade. Considerable structural information is available for the motor domain, the IQ motifs with bound calmodulin or light
chains, and the cargo-binding globular tail, all of which have been crystallized. The repertoire of adapter proteins that
link myoV to a particular cargo is becoming better understood, enabling cellular transport processes to be dissected. MyoV
is processive, meaning that it takes many steps on actin filaments without dissociating. Its extended lever arm results in
long 36-nm steps, making it ideal for single molecule studies of processive movement. In addition, electron microscopy revealed
the structure of the inactive, folded conformation of myoV when it is not transporting cargo. This review provides a background
on myoV, and highlights recent discoveries that show why myoV will continue to be an active focus of investigation.
Received 31 October 2007; received after revision 4 December 2007; accepted 2 January 2008 相似文献
9.
At the moment of insemination millions of mammalian sperm cells are released into the female reproductive tract in order to
find a single cell – the oocyte. The spermatozoa subsequently ignore the thousands of cells they make contact with during
their journey to the site of fertilisation, until they reach the surface of the oocyte. At this point, they bind tenaciously
to the acellular coat, known as the zona pellucida, that surrounds the oocyte and initiate the chain of cellular interactions
that will culminate in fertilization. These exquisitely cell- and species-specific recognition events are among the most strategically
important cellular interactions in biology. Understanding the cellular and molecular mechanisms that underpin them has implications
for diagnosis of the aetiology of human infertility and the development of novel targets for fertility regulation. Herein,
we describe two models indicating the plethora of highly orchestrated molecular interactions underlying successful sperm zona
binding and sperm oocyte fusion.
Received 17 December 2006; received after revision 31 January 2007; accepted 16 March 2007 相似文献
10.
Sumoylation regulates diverse biological processes 总被引:8,自引:0,他引:8
Zhao J 《Cellular and molecular life sciences : CMLS》2007,64(23):3017-3033
Ten years after its discovery, the small ubiquitin-like protein modifier (SUMO) has emerged as a key regulator of proteins.
While early studies indicated that sumoylation takes place mainly in the nucleus, an increasing number of non-nuclear substrates
have recently been identified, suggesting a wider stage for sumoylation in the cell. Unlike ubiquitylation, which primarily
targets a substrate for degradation, sumoylation regulates a substrate’s functions mainly by altering the intracellular localization,
protein-protein interactions or other types of post-translational modifications. These changes in turn affect gene expression,
genomic and chromosomal stability and integrity, and signal transduction. Sumoylation is counter-balanced by desumoylation,
and well-balanced sumoylation is essential for normal cellular behaviors. Loss of the balance has been associated with a number
of diseases. This paper reviews recent progress in the study of SUMO pathways, substrates, and cellular functions and highlights
important findings that have accelerated advances in this study field and link sumoylation to human diseases.
Received 19 March 2007; received after version 16 July 2007; accepted 1 August 2007 相似文献
11.
The RecQ family of DNA helicases is highly conserved throughout evolution and plays an important role in the maintenance of
genomic stability in all organisms. Mutations in three of the five known family members in humans, BLM, WRN and RECQL4, give rise to disorders that are characterized by predisposition to cancer and premature aging, emphasizing the importance
of studying the RecQ proteins and their cellular activities. Interestingly, three autosomal recessive disorders have been
associated with mutations in the RECQL4 gene: Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes, thus making RECQL4 unique within the RecQ family of DNA
helicases. To date, however, the molecular function of RECQL4 and the possible cellular pathways in which it is involved remain
poorly understood. Here, we present an overview of recent findings in connection with RECQL4 and try to highlight different
directions the field could head, helping to clarify the role of RECQL4 in preventing tumorigenesis and maintenance of genome
integrity in humans.
Received 31 October 2006; received after revision 4 January 2007; accepted 5 February 2007 相似文献
12.
Olfactory ensheathing cells have been used in several studies to promote repair in the injured spinal cord. However, cellular
interaction between olfactory ensheathing cells and glial cells induced to be reactive in the aftermath of injury site has
not been investigated. Using an in vitro model of astrogliosis, we show that reactive astrocytes expressed significantly less glial fibrillary acidic protein (GFAP)
when cultured both in direct contact with olfactory ensheathing cells and when the two cell types were separated by a porous
membrane. Immunofluorescence staining also suggested that reactive astrocytes showed decreased chondroitin sulfate proteoglycans
in the presence of olfactory ensheathing cells, although the reduction was not statistically significant. No down-regulation
of GFAP was observed when reactive astrocytes were similarly cultured with Schwann cells. Cell viability assay and bromodeoxyuridine
uptake showed that proliferation of reactive astrocytes was significantly increased in the presence of olfactory ensheathing
cells and Schwann cells.
Received 27 February 2007; received after revision 30 March 2007; accepted 3 April 2007 相似文献
13.
Zazímalová E Krecek P Skůpa P Hoyerová K Petrásek J 《Cellular and molecular life sciences : CMLS》2007,64(13):1621-1637
The PIN-FORMED (PIN) protein family is a group of plant transmembrane proteins with a predicted function as secondary transporters.
PINs have been shown to play a rate-limiting role in the catalysis of efflux of the plant growth regulator auxin from cells,
and their asymmetrical cellular localization determines the direction of cell-to-cell auxin flow. There is a functional redundancy
of PINs and their biochemical activity is regulated at many levels. PINs constitute a flexible network underlying the directional
auxin flux (polar auxin transport) which provides cells in any part of the plant body with particular positional and temporal
information. Thus, the PIN network, together with downstream auxin signalling system(s), coordinates plant development. This
review summarizes recent progress in the elucidation of the role of PIN proteins in polar auxin transport at the cellular
level, with emphasis on their structure and evolution and regulation of their function.
Received 28 December 2006; received after revision 16 February 2007; accepted 26 March 2007 相似文献
14.
Computational inhibitor design against malaria plasmepsins 总被引:1,自引:1,他引:0
Bjelic S Nervall M Gutiérrez-de-Terán H Ersmark K Hallberg A Aqvist J 《Cellular and molecular life sciences : CMLS》2007,64(17):2285-2305
Plasmepsins are aspartic proteases involved in the degradation of the host cell hemoglobin that is used as a food source by
the malaria parasite. Plasmepsins are highly promising as drug targets, especially when combined with the inhibition of falcipains
that are also involved in hemoglobin catabolism. In this review, we discuss the mechanism of plasmepsins I–IV in view of the
interest in transition state mimetics as potential compounds for lead development. Inhibitor development against plasmepsin
II as well as relevant crystal structures are summarized in order to give an overview of the field. Application of computational
techniques, especially binding affinity prediction by the linear interaction energy method, in the development of malarial
plasmepsin inhibitors has been highly successful and is discussed in detail. Homology modeling and molecular docking have
been useful in the current inhibitor design project, and the combination of such methods with binding free energy calculations
is analyzed.
S. Bjelic, M. Nervall: These authors contributed equally to this work.
Received 27 February 2007; received after revision 17 April 2007; accepted 26 April 2007 相似文献
15.
Obesity is a multifactorial and heterogeneous condition that results from alterations of various genes, each having a partial
and additive effect. The inheritance pattern of obesity is thus complex, and environmental factors play an important role
in promoting or delaying its development. The identification of susceptibility genes and genetic variants for obesity requires
various methodological approaches. Obesity is classified into three main categories on the basis of genetic etiology: monogenic,
syndromic, and polygenic obesity. Here we review monogenic and syndromic obesity. We also review the linkage analysis studies
followed by the candidate gene approaches and genome-wide association studies. Identification of the underlying genetic causes
of obesity will likely provide a basis both for the development of new therapeutic agents and for the personalized prevention
of this condition.
Received 2 October 2007; received after revision 15 November 2007; accepted 19 November 2007 相似文献
16.
Rauch U 《Cellular and molecular life sciences : CMLS》2004,61(16):2031-2045
In the central nervous system, various extracellular matrix components have been identified which are strongly expressed during development and in most areas of the brain down-regulated during maturation. Examples are tenascin-C, neurocan and hyaluronan. While tenascin-C is well known to be associated with morphogenic events and the active contribution of hyaluronan to various physiological processes is increasingly acknowledged, neurocan belongs to a class of molecules thought to be generally more associated with barrier functions: chondroitin sulfate proteoglycans. Consideration of these and related molecules and their processing in the context of the general organization of the brain extracellular matrix, their changes during brain maturation and their implication in different types of remodeling processes in adult brain, like normal and pathological synaptic plasticity, inflammatory and dementia-associated diseases and gliomas, may indicate that components of the extracellular matrix could provide valuable early information about the pathological state of the brain.Received 29 January 2004; received after revision 25 March 2004; accepted 2 April 2004 相似文献
17.
Ramirez F Sakai LY Rifkin DB Dietz HC 《Cellular and molecular life sciences : CMLS》2007,64(18):2437-2446
Fibrillins are the structural components of extracellular microfibrils that impart physical properties to tissues, alone or
together with elastin as elastic fibers. Genetic studies in mice have revealed that fibrillin-rich microfibrils are also involved
in regulating developmental programs and homeostatic processes through the modulation of TGF-β/BMP signaling events. A new
paradigm has thus emerged whereby the spatiotemporal organization of microfibrils dictates both the cellular activities and
physical properties of connective tissues. These observations have paved the way to novel therapeutic approaches aimed at
counteracting the life-threatening complications in human conditions caused by dysfunctions of fibrillin-rich microfibrils.
Received 2 April 2007; received after revision 23 May 2007; accepted 24 May 2007 相似文献
18.
The highly conserved Notch signaling pathway plays pleiotropic roles during embryonic development and is important for the
regulation of selfrenewing tissues. The physiological functions of this signaling cascade range from stem cell maintenance
and influencing cell fate decisions of barely differentiated progenitor cells, to the induction of terminal differentiation
processes, all of which have been found to be recapitulated in different forms of cancers. Although Notch signaling has mostly
been associated with oncogenic and growth-promoting roles, depending on the tissue type it can also function as a tumor suppressor.
Here we describe recent findings on Notch signaling in cancer and tumor angiogenesis, and highlight some of the therapeutic
approaches that are currently being developed to interfere with tumor growth and progression.
Received 2 April 2007; received after revision 29 June 2007; accepted 2 July 2007 相似文献
19.
Towards progress on DNA vaccines for cancer 总被引:2,自引:0,他引:2
Lowe DB Shearer MH Jumper CA Kennedy RC 《Cellular and molecular life sciences : CMLS》2007,64(18):2391-2403
Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived
immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA
represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response
in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed
well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not
impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing
DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid
DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response
while also targeting tumor evasion mechanisms.
Received 2 April 2007; received after revision 14 May 2007; accepted 21 May 2007 相似文献
20.
The recent development of functional models to analyze the early steps of the hepatitis C virus (HCV) life cycle has highlighted
that HCV entry is a slow and complex multistep process involving the presence of several entry factors. Initial host cell
attachment may involve glycosaminoglycans and the low-density lipoprotein receptor, after which the particle appears to interact
sequentially with three entry factors: the scavenger receptor class B type I, the tetraspanin CD81 and the tight-junction
protein claudin-1. Several serum components may also modulate HCV entry, while the recently discovered CD81 partner EWI-2wint
can block the interaction of the viral particle with CD81, potentially preventing infection in the cell types in which it
is expressed. After binding to the host cell, the HCV particle is internalized by clathrin-mediated endocytosis, with fusion
likely occuring in early endosomes. This review summarizes our current knowledge on HCV entry.
Received 27 June 2007; received after revision 2 August 2007; accepted 29 August 2007 相似文献