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951.
Nodal signals pattern vertebrate embryos 总被引:4,自引:0,他引:4
Vertebrate embryonic patterning requires several conserved inductive signals–including Nodal, Bmp, Wnt and Fgf signals. Nodal,
which is a member of the transforming growth factor β (TGFβ) superfamily, activates a signal transduction pathway that is
similar to that of other TGFβ members. Nodal genes, which have been identified in numerous vertebrate species, are expressed
in specific cell types and tissues during embryonic development. Nodal signal transduction has been shown to play a pivotal
role in inducing and patterning mesoderm and endoderm, and in regulating neurogenesis and left-right axis asymmetry. Antagonists,
which act at different steps in the Nodal signal transduction pathway, have been shown to tightly modulate the inductive activity
of Nodal.
Received 20 October 2005; received after revision 15 November 2005; accepted 25 November 2005 相似文献
952.
Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines, in proteins has been directly implicated in
various degenerative diseases through a mechanism of protein misfolding and aggregation. However, it is still unclear how
the nature of the expansion and the protein context influence the tendency of a protein to aggregate. Here, we have addressed
these questions using spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the polyglutamine proteins,
chosen as a model system. Using a transfected mammalian cell line, we demonstrate that ATX3 aggregation is noticeably reduced
by deletion or replacement of regions other than the polyglutamine tract. The nature of the amino acid homo-sequences also
has a strong influence on aggregation. From our studies, we draw general conclusions on the effect of the protein architecture
and of the amino acid homo-sequence on pathology.
Received 3 March 2006; received after revision 19 April 2006; accepted 22 May 2006 相似文献
953.
Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? 总被引:1,自引:0,他引:1
Betaine homocysteine methyltransferase (BHMT), a Zn2+-dependent thiolmethyltransferase, contributes to the regulation of homocysteine levels, increases in which are considered
a risk factor for cardiovascular diseases. Most plasma homocysteine is generated through the liver methionine cycle, in which
BHMT metabolizes approximately 25% of this non-protein amino acid. This process allows recovery of one of the three methylation
equivalents used in phosphatidylcholine synthesis through transmethylation, a major homocysteine-producing pathway. Although
BHMT has been known for over 40 years, the difficulties encountered in its isolation precluded detailed studies until very
recently. Thus, the last 10 years, since the sequence became available, have yielded extensive structural and functional data.
Moreover, recent findings offer clues for potential new functions for BHMT. The purpose of this review is to provide an integrated
view of the knowledge available on BHMT, and to analyze its putative roles in other processes through interactions uncover
to date.
Received 26 May 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
954.
Bosch-Comas A Lindsten K Gonzàlez-Duarte R Masucci MG Marfany G 《Cellular and molecular life sciences : CMLS》2006,63(6):723-734
The biological functions of the more than one hundred genes coding for deubiquitinating enzymes in the human genome remain
mostly unknown. The USP25 gene, located at 21q11.2, encodes three protein isoforms produced by alternative splicing. While
two of the isoforms are expressed nearly ubiquituously, the expression of the longer USP25 isoform (USP25m) is restricted
to muscular tissues and is upregulated during myogenesis. USP25m interacts with three sarcomeric proteins: actin alpha-1 (ACTA1),
filamin C (FLNC), and myosin binding protein C1 (MyBPC1), which are critically involved in muscle differentiation and maintenance,
and have been implicated in the pathogenesis of severe myopathies. Biochemical analyses demonstrated that MyBPC1 is a short-lived
proteasomal substrate, and its degradation is prevented by over-expression of USP25m but not by other USP25 isoforms. In contrast,
ACTA1 and FLNC appear to be stable proteins, indicating that their interaction with USP25m is not related to their turnover
rate.
Received 7 November 2005; received after revision 7 January 2006; accepted 13 January 2006 相似文献
955.
Temussi PA 《Cellular and molecular life sciences : CMLS》2006,63(16):1876-1888
A few proteins, discovered mainly in tropical fruits, have a distinct sweet taste. These proteins have played an important
role towards a molecular understanding of the mechanisms of taste. Owing to the huge difference in size, between most sweeteners
and sweet proteins, it was believed that they must interact with a different receptor from that of small molecular weight
sweeteners. Recent modelling studies have shown that the single sweet taste receptor has multiple active sites and that the
mechanism of interaction of sweet proteins is intrinsically different from that of small sweeteners. Small molecular weight
sweeteners occupy small receptor cavities inside two subdomains of the receptor, whereas sweet proteins can interact with
the sweet receptor according to a mechanism called the ‘wedge model’ in which they bind to a large external cavity. This review
describes these mechanisms and outlines a history of sweet proteins.
Received 11 February 2006; received after revision 31 March 2006; accepted 11 May 2006 相似文献
956.
957.
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis 总被引:21,自引:0,他引:21
Palmer CN Irvine AD Terron-Kwiatkowski A Zhao Y Liao H Lee SP Goudie DR Sandilands A Campbell LE Smith FJ O'Regan GM Watson RM Cecil JE Bale SJ Compton JG DiGiovanna JJ Fleckman P Lewis-Jones S Arseculeratne G Sergeant A Munro CS El Houate B McElreavey K Halkjaer LB Bisgaard H Mukhopadhyay S McLean WH 《Nature genetics》2006,38(4):441-446
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease. 相似文献
958.
The detection of sequence variation, for which DNA sequencing has emerged as the most sensitive and automated approach, forms the basis of all genetic analysis. Here we describe and illustrate an algorithm that accurately detects and genotypes SNPs from fluorescence-based sequence data. Because the algorithm focuses particularly on detecting SNPs through the identification of heterozygous individuals, it is especially well suited to the detection of SNPs in diploid samples obtained after DNA amplification. It is substantially more accurate than existing approaches and, notably, provides a useful quantitative measure of its confidence in each potential SNP detected and in each genotype called. Calls assigned the highest confidence are sufficiently reliable to remove the need for manual review in several contexts. For example, for sequence data from 47-90 individuals sequenced on both the forward and reverse strands, the highest-confidence calls from our algorithm detected 93% of all SNPs and 100% of high-frequency SNPs, with no false positive SNPs identified and 99.9% genotyping accuracy. This algorithm is implemented in a software package, PolyPhred version 5.0, which is freely available for academic use. 相似文献
959.
Foser S Redwanz I Ebeling M Heizmann CW Certa U 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2387-2396
A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-alpha and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A DNA microarray-based search for proliferation control genes involved that are cooperatively activated by IFN-alpha and TGF-beta, yielded 28 genes. Among these are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium-binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a potent growth inhibitor requiring TGF-beta activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-alpha and TGF-beta signaling and extends the function of IFN signaling to calcium-sensitive processes. 相似文献
960.
Catassi A Cesario A Arzani D Menichini P Alama A Bruzzo C Imperatori A Rotolo N Granone P Russo P 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2377-2386
The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells, GADD45alpha-gamma and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial 'intrinsic' pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-kappaB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs. 相似文献