排序方式: 共有63条查询结果,搜索用时 31 毫秒
11.
Vonk WI de Bie P Wichers CG van den Berghe PV van der Plaats R Berger R Wijmenga C Klomp LW van de Sluis B 《Cellular and molecular life sciences : CMLS》2012,69(1):149-163
Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function
of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described.
A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied
displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting
capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells
at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded
ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A
function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to
adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting
activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data
might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant
proteins, and suggests a potential role for COMMD1 in this process. 相似文献
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Janesh Pillay Tamar Tak Vera M. Kamp Leo Koenderman 《Cellular and molecular life sciences : CMLS》2013,70(20):3813-3827
Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research. 相似文献
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Gissen P Johnson CA Morgan NV Stapelbroek JM Forshew T Cooper WN McKiernan PJ Klomp LW Morris AA Wraith JE McClean P Lynch SA Thompson RJ Lo B Quarrell OW Di Rocco M Trembath RC Mandel H Wali S Karet FE Knisely AS Houwen RH Kelly DA Maher ER 《Nature genetics》2004,36(4):400-404
ARC syndrome (OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life. To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion. 相似文献
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van Overveld PG Lemmers RJ Sandkuijl LA Enthoven L Winokur ST Bakels F Padberg GW van Ommen GJ Frants RR van der Maarel SM 《Nature genetics》2003,35(4):315-317
The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD1, OMIM 158900) is caused by contraction of the D4Z4 repeat array on 4qter. We show that this contraction causes marked hypomethylation of the contracted D4Z4 allele in individuals with FSHD1. Individuals with phenotypic FSHD1, who are clinically identical to FSHD1 but have an unaltered D4Z4, also have hypomethylation of D4Z4. These results strongly suggest that hypomethylation of D4Z4 is a key event in the cascade of epigenetic events causing FSHD1. 相似文献
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Carlton JM Angiuoli SV Suh BB Kooij TW Pertea M Silva JC Ermolaeva MD Allen JE Selengut JD Koo HL Peterson JD Pop M Kosack DS Shumway MF Bidwell SL Shallom SJ van Aken SE Riedmuller SB Feldblyum TV Cho JK Quackenbush J Sedegah M Shoaibi A Cummings LM Florens L Yates JR Raine JD Sinden RE Harris MA Cunningham DA Preiser PR Bergman LW Vaidya AB van Lin LH Janse CJ Waters AP Smith HO White OR Salzberg SL Venter JC Fraser CM Hoffman SL Gardner MJ Carucci DJ 《Nature》2002,419(6906):512-519
Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease. 相似文献
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Dominant effector genetics in mammalian cells 总被引:6,自引:0,他引:6
Xu X Leo C Jang Y Chan E Padilla D Huang BC Lin T Gururaja T Hitoshi Y Lorens JB Anderson DC Sikic B Luo Y Payan DG Nolan GP 《Nature genetics》2001,27(1):23-29
We have expressed libraries of peptides in mammalian cells to select for trans-dominant effects on intracellular signaling systems. As an example-and to reveal pharmacologically relevant points in pathways that lead to Taxol resistance-we selected for peptide motifs that confer resistance to Taxol-induced cell death. Of several peptides selected, one, termed RGP8.5, was linked to upregulation of expression of the gene ABCB1 (also known as MDR1, for multiple drug resistance) in HeLa cells. Our data indicate that trans-dominant effector peptides can point to potential mechanisms by which signaling systems operate. Such tools may be useful in functional genomic analysis of signaling pathways in mammalian disease processes. 相似文献
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Direct generation of functional dopaminergic neurons from mouse and human fibroblasts 总被引:2,自引:0,他引:2