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951.
Myelin basic protein: a multifunctional protein 总被引:1,自引:1,他引:0
Boggs JM 《Cellular and molecular life sciences : CMLS》2006,63(17):1945-1961
Myelin basic protein (MBP), the second most abundant protein in central nervous system myelin, is responsible for adhesion
of the cytosolic surfaces of multilayered compact myelin. A member of the ‘intrinsically disordered’ or conformationally adaptable
protein family, it also appears to have several other functions. It can interact with a number of polyanionic proteins including
actin, tubulin, Ca2+-calmodulin, and clathrin, and negatively charged lipids, and acquires structure on binding to them. It may act as a membrane
actin-binding protein, which might allow it to participate in transmission of extracellular signals to the cytoskeleton in
oligodendrocytes and tight junctions in myelin. Some size isoforms of MBP are transported into the nucleus and thus they may
also bind polynucleotides. Extracellular signals received by myelin or cultured oligodendrocytes cause changes in phosphorylation
of MBP, suggesting that MBP is also involved in signaling. Further study of this very abundant protein will reveal how it
is utilized by the oligodendrocyte and myelin for different purposes.
Received 2 March 2006; received after revision 12 April 2006; accepted 16 May 2006 相似文献
952.
Based on the classification of bacterial lipolytic enzymes, family I.3 lipase is a member of the large group of Gram-negative
bacterial true lipases. This lipase family is distinguished from other families not only by the amino acid sequence, but also
by the secretion mechanism. Lipases of family I.3 are secreted via the well-known type I secretion system. Like most of proteins
secreted via this system, family I.3 lipases are composed of two domains with distinct yet related functions. Recent years
have seen an increasing amount of research on this lipase family, in terms of isolation, secretion mechanism, as well as biochemical
and biophysical studies. This review describes our current knowledge on the structure-function relationships of family I.3
lipase, with an emphasis on its secretion mechanism.
Received 18 April 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
953.
Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic
acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place
by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a
general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease,
belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended
our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will
centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human
disease and the way it is produced from phytol.
Received 4 October 2005; received after revision 24 February 2006; accepted 26 April 2006 相似文献
954.
McTaggart SJ 《Cellular and molecular life sciences : CMLS》2006,63(3):255-267
Isoprenoids are synthesized in all living organisms and are incorporated into diverse classes of end-products that participate
in a multitude of cellular processes relating to cell growth, differentiation, cytoskeletal function and vesicle trafficking.
In humans, the non-sterol isoprenoids, farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, are synthesized via the mevalonate
pathway and are covalently added to members of the small G protein superfamily. Isoprenylated proteins have key roles in membrane
attachment and protein functionality, have been shown to have a central role in some cancers and are likely also to be involved
in the pathogenesis and progression of atherosclerosis and Alzheimer disease. This review details current knowledge on the
biosynthesis of isoprenoids, their incorporation into proteins by the process known as prenylation and the complex regulatory
network that controls these proteins. An improved understanding of these processe is likely to lead to the development of
novel therapies that will have important implications for human health and disease.
Received 5 July 2005; received after revision 17 October 2005; accepted 22 October 2005 相似文献
955.
Memories become stabilized through a time-dependent process that requires gene expression and is commonly known as consolidation. During this time, memories are labile and can be disrupted by a number of interfering events, including electroconvulsive shock, trauma and other learning or the transient effect of drugs such as protein synthesis inhibitors. Once consolidated, memories are insensitive to these disruptions. However, they can again become fragile if recalled or reactivated. Reactivation creates another time-dependent process, known as reconsolidation, during which the memory is restabilized. Here we discuss some of the questions currently debated in the field of memory consolidation and reconsolidation, the molecular and anatomical requirements for both processes and, finally, their functional relationship. 相似文献
956.
957.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681
958.
959.
Recent experience with several high-profile drugs demonstrates the great challenges in developing effective and safe therapeutics. A complementary approach to the popular paradigm of disease genetics is based on inherited factors that reduce the incidence and severity of disease among individuals who are genetically predisposed to disease. We propose testing specifically for modifier genes and protective alleles among at-risk individuals and studying the efficacy of therapeutics based on the genetics of health. 相似文献
960.
Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration 总被引:12,自引:0,他引:12
Maller J George S Purcell S Fagerness J Altshuler D Daly MJ Seddon JM 《Nature genetics》2006,38(9):1055-1059
Age-related macular degeneration (AMD) is a common, late-onset disease with seemingly typical complexity: recurrence ratios for siblings of an affected individual are three- to sixfold higher than in the general population, and family-based analysis has resulted in only modestly significant evidence for linkage. In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes (P values ranging from 10(-6) to 10(-70)). Despite excellent power to detect epistasis, we observed purely additive accumulation of risk from alleles at these genes. We found no differences in association of these loci with major phenotypic categories of advanced AMD. Genotypes at these five common SNPs define a broad spectrum of interindividual disease risk and explain about half of the classical sibling risk of AMD in our study population. 相似文献