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1.
Interest in the glycerophosphoinositols has been increasing recently, on the basis of their biological activities. The cellular metabolism of these water-soluble bioactive phosphoinositide metabolites has been clarified, with the identification of the specific enzyme involved in their synthesis, PLA2IVα (phospholipase A2 IVα), and the definition of their phosphodiesterase-based catabolism, and thus inactivation. The functional roles and mechanisms of action of these compounds have been investigated in different cellular contexts. This has led to their definition in the control of various cell functions, such as cell proliferation in the thyroid and actin cytoskeleton organization in fibroblasts and lymphocytes. Roles for the glycerophosphoinositols in immune and inflammatory responses are also being defined. In addition to these physiological functions, the glycerophosphoinositols have potential anti-metastatic activities that should lead to their pharmacological exploitation.  相似文献   

2.
Recently produced information on post-translational modifications makes it possible to interpret their biological regulation with new insights. Various protein modifications finely tune the cellular functions of each protein. Understanding the relationship between post-translational modifications and functional changes ("post-translatomics") is another enormous project, not unlike the human genome project. Proteomics, combined with separation technology and mass spectrometry, makes it possible to dissect and characterize the individual parts of post-translational modifications and provide a systemic analysis. Systemic analysis of post-translational modifications in various signaling pathways has been applied to illustrate the kinetics of modifications. Availability will advance new technologies that improve sensitivity and peptide coverage. The progress of "post-translatomics", novel analytical technologies that are rapidly emerging, offer a great potential for determining the details of the modification sites.  相似文献   

3.
The structure of tubulin has recently been determined by electron crystallography, paving the way for a clearer understandin of the unique properties of tubulin that allow its varied functions within the cell. Some of the ongoing work on tubulin can be interpreted in terms of its structure, which can serve to guide future studies.  相似文献   

4.
Histones and their modifications   总被引:39,自引:0,他引:39  
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5.
Genetic modifications during cellular aging   总被引:3,自引:0,他引:3  
Summary We review evidence that biological aging is a genetic process related to development and cytodifferentiation and thus may involve alterations of DNA structure and gene expression. We conclude that although determined to a high degree aging also involves stochastic features which lead to progressive somatic cell diversification during the life span. These considerations may help to explain the unevenness of physiological decline and the clonal emergence of certain age-dependent diseases such as cancer.  相似文献   

6.
The large number of different membrane lipids with various structural modifications and properties and the characteristic lipid composition of different types of membranes suggest that different lipids have specific functions in the membrane. Many of the varying properties of lipids with different polar head groups and in different ionization states can be attributed to the presence of interactive or repulsive forces between the head groups in the bilayer. The interactive forces are hydrogen bonds between hydrogen bond donating groups such as --P--OH,--OH, and--NH3+ and hydrogen bond accepting groups such as --P--O- and --COO-. These interactions increase the lipid phase transition temperature and can account for the tendency of certain lipids to go into the hexagonal phase and the dependence of this tendency on the pH and ionization state of the lipid. The presence or absence of these interactions can also affect the penetration of hydrophobic substances into the bilayer, including hydrophobic residues of membrane proteins. Evidence for this suggestion has been gathered from studies of the myelin basic protein, a water-soluble protein with a number of hydrophobic residues. In this way the lipid composition can affect the conformation and activity of membrane proteins. Since hydrogen-bonding interactions depend on the ionization state of the lipid, they can be altered by changes in the environment which affect the pK of the ionizable groups. The formation of the hexagonal phase or inverted micelles, the conformation and activity of membrane proteins, and other functions mediated by lipids could thus be regulated in this way.  相似文献   

7.
Chromatin modifications and their function   总被引:99,自引:0,他引:99  
Kouzarides T 《Cell》2007,128(4):693-705
The surface of nucleosomes is studded with a multiplicity of modifications. At least eight different classes have been characterized to date and many different sites have been identified for each class. Operationally, modifications function either by disrupting chromatin contacts or by affecting the recruitment of nonhistone proteins to chromatin. Their presence on histones can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA. In this way, histone modifications have the potential to influence many fundamental biological processes, some of which may be epigenetically inherited.  相似文献   

8.
Hyder CL  Pallari HM  Kochin V  Eriksson JE 《FEBS letters》2008,582(14):2140-2148
Intermediate filaments are dynamically regulated by their post-translational modifications. Initially these modifications were found to regulate filament dynamics and organization. In the last few years, their roles have extended significantly to facilitating, for example, the recruitment and sequestration of signaling molecules that regulate a wide range of cellular functions. While phosphorylation has been established as the principal post-translational modification regulating intermediate filament function, other modifications with co-operative roles are emerging, adding a further dimensions to intermediate filament-mediated signaling.  相似文献   

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11.
Robustness of cellular functions   总被引:35,自引:0,他引:35  
Stelling J  Sauer U  Szallasi Z  Doyle FJ  Doyle J 《Cell》2004,118(6):675-685
Robustness, the ability to maintain performance in the face of perturbations and uncertainty, is a long-recognized key property of living systems. Owing to intimate links to cellular complexity, however, its molecular and cellular basis has only recently begun to be understood. Theoretical approaches to complex engineered systems can provide guidelines for investigating cellular robustness because biology and engineering employ a common set of basic mechanisms in different combinations. Robustness may be a key to understanding cellular complexity, elucidating design principles, and fostering closer interactions between experimentation and theory.  相似文献   

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15.
Multiple fibronectin subunits and their post-translational modifications   总被引:11,自引:0,他引:11  
We report analyses of fibronectin subunit diversity by high resolution one- and two-dimensional gel electrophoresis. We have studied plasma and cellular fibronectins of rats and hamsters. Each form of fibronectin comprises multiple distinguishable subunits and, within each rodent species, all subunits of plasma fibronectin are resolvable from those of cellular fibronectin. Some, but not all, of this heterogeneity is caused by differential glycosylation. Thus, while glycosylated plasma and cellular fibronectins share no common subunits, nonglycosylated forms of these proteins appear to share 2-3 subunits. In addition, there are subunits unique to plasma and to cellular fibronectins in both rats and hamsters, although the pattern of diversity differs slightly between species. All size variants of fibronectin are phosphorylated to varying degrees. However, only some subunits are sulfated, apparently on tyrosine residues in the C-terminal third of the molecule. Comparison of the distribution of sulfate on the various fibronectin subunits with recent results on generation of multiple mRNAs by alternative splicing suggests that tyrosine sulfate is located in a polypeptide segment present in only certain fibronectin subunits. The results reported here provide information on the likely contributions of primary sequence differences and post-translational modifications to the heterogeneity of fibronectin subunits.  相似文献   

16.
Peptide nucleic acids and their structural modifications   总被引:3,自引:0,他引:3  
Peptide (polyamide) analogues of nucleic acids (PNAs) make very promising groups of natural nucleic acid (NA) ligands and show many other interesting properties. Two types of these analogues may be highlighted as particularly interesting: the first, containing a polyamide with alternating peptide/pseudopeptide bonds as its backbone, consisting of N-(aminoalkyl)amino-acid units (type I), with nucleobases attached to the backbone nitrogen with the carboxyalkyl linker; and the second, containing a backbone consisting of amino-acid residues carrying the nucleobases in their side chains (type II). So far, these two groups have been studied most intensively. The paper describes main groups of peptide nucleic acids, as well as various other amino acid-derived nucleobase monomers or their oligomers, which were either studied in order to determine their hybridisation to nucleic acids, or only discussed with respect to their potential usefulness in the oligomerisation and nucleic acids binding.  相似文献   

17.
The common assumption of operons as composed of genes that cooperate in a biological process is confirmed here by showing that Escherichia coli operons tend to be composed of genes that belong to the same general class of cellular function. Furthermore, the comparison between the genomic organization of E. coli and that of Bacillus subtilis shows that the genes that are homologous to genes that belong to experimentally characterized E. coli operons tend to cluster in neighboring regions of the genome. This tendency is greater for the subset of E. coli operons whose genes belong to a single functional class. These observations indicate strong evolutionary pressure that, translated into functional constraints, leads to the inclusion of many essential functions in conserved operons and clusters in these two distant species.  相似文献   

18.
ABSTRACT: Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitors (PIs) are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that block HIV-1 protease active site, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS) system, thus increasing the chance of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of fission yeast as a possible surrogate system to study the effects of HIV-1 protease on cellular functions and to explore its utility as a HTS system to search for new PIs to battle HIV-1 strains resistant to the current PI drugs.  相似文献   

19.
Microtubules are subject to a variety of posttranslational modifications that potentially regulate cytoskeletal functions. Two modifications, glutamylation and glycylation, are highly enriched in the axonemes of most eukaryotes, and might therefore play particularly important roles in cilia and flagella. Here we systematically analyze the dynamics of glutamylation and glycylation in developing mouse ependymal cilia and the expression of the corresponding enzymes in the brain. By systematically screening enzymes of the TTLL family for specific functions in ependymal cilia, we demonstrate that the glycylating enzymes TTLL3 and TTLL8 were required for stability and maintenance of ependymal cilia, whereas the polyglutamylase TTLL6 was necessary for coordinated beating behavior. Our work provides evidence for a functional separation of glutamylating and glycylating enzymes in mammalian ependymal cilia. It further advances the elucidation of the functions of tubulin posttranslational modifications in motile cilia of the mammalian brain and their potential importance in brain development and disease.  相似文献   

20.
In this review we summarize and generalize the recent data on structure, regulation and physiological role of calcium/calmodulin-dependent protein kinases, or CaM kinases. CaM kinases are the family of structurally homologous enzymes, involved into a variety of Ca(2+)-induced cellular reactions through phosphorylation of target proteins. In recent years the quantity of these enzymes has exceeded twenty, mainly due to identification of new isozymic forms of already known CaM kinases. Using crystal structure analysis data, some researchers constructed molecular models of regulation and functioning of CaM kinases. Many reports of recent years are devoted to investigation of functions of CaM kinase isozymes and their role in various cellular processes.  相似文献   

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