排序方式: 共有72条查询结果,搜索用时 15 毫秒
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Chiung-Mei Chen I-Cheng Chen Yi-Cheng Huang Hsueh-Fen Juan Ying-Lin Chen Yi-Chun Chen Chih-Hsin Lin Li-Ching Lee Chi-Mei Lee Guey-Jen Lee-Chen Yun-Ju Lai Yih-Ru Wu 《PloS one》2014,9(7)
Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson''s disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤50) and only two known variants, Y52C (c.155A>G) and M115I (c.345G>A), were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case–control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012) and significant association of G allele with decreased PD risk (p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2) was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese. 相似文献
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Linda May Anita HJ van den Biggelaar David van Bodegom Hans J Meij Anton JM de Craen Joseph Amankwa Marijke Frölich Maris Kuningas Rudi GJ Westendorp 《Immunity & ageing : I & A》2009,6(1):1-7
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. The aim of this work was to compile a comprehensive literature review of the clinical features and genetic mutations and mechanisms of this syndrome as a contribution to health care workers. This review shows the necessity of a more detailed clinical identification of Hutchinson-Gilford progeria syndrome and the need for more studies on the pharmacologic and pharmacogenomic approach to this syndrome. 相似文献
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Freshwater crayfish invasions have been studied around the world, but less so in Africa, a continent devoid of native freshwater crayfish. The present study reviews historical and current information on alien freshwater crayfish species introduced into South Africa and aims to indicate which areas are at risk from invasion. As is the case elsewhere, South Africans have shown a keen interest in both farming and keeping freshwater crayfish as pets, which has resulted in Cherax cainii, Cherax destructor, Cherax quadricarinatus and Procambarus clarkii being introduced to the country. There is evidence of successful establishment in the wild for C. quadricarinatus and P. clarkii in different parts of the country. Species distribution models suggest that the eastern part of the country and parts of the Eastern and Western Cape are at higher risk of invasion. At present, illegal translocations represent the most likely pathway of crayfish spread in South Africa. A continued risk of invasion by freshwater crayfish species in South Africa is highlighted, which reinforces the need for more research, as well as for strong mitigation measures, such as stronger policing of existing regulations, management or eradication where feasible and public education. 相似文献
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Background
The pagN gene of Salmonella enterica serovar Typhimurium is a PhoP-regulated gene that is up-regulated during growth within macrophages and in vivo in murine models of infection. The PagN protein displays similarity to the Hek and Tia invasins/adhesins of Escherichia coli. Thus far no function has been ascribed to the PagN protein. 相似文献46.
Leon GJ Tertoolen Christophe Blanchetot Guoqiang Jiang John Overvoorde Theodorus WJ Gadella Jr Tony Hunter Jeroen den Hertog 《BMC cell biology》2001,2(1):8-14
Background
Dimerization is an important regulatory mechanism of single membrane-spanning receptors. For instance, activation of receptor protein-tyrosine kinases (RPTKs) involves dimerization. Structural, functional and biochemical studies suggested that the enzymatic counterparts of RPTKs, the receptor protein-tyrosine phosphatases (RPTPs), are inhibited by dimerization, but whether RPTPs actually dimerize in living cells remained to be determined. 相似文献47.
Chih-Hsin Lin Chiung-Mei Chen Yi-Ting Hou Yih-Ru Wu Hsiu-Mei Hsieh-Li Ming-Tsan Su Guey-Jen Lee-Chen 《Human genetics》2010,128(2):205-212
PPP2R2B, a protein widely expressed in neurons, regulates the protein phosphatase 2A (PP2A) activity for dephosphorylation
of tau and other substrates. CAG repeat expansion at the 5′-end of the PPP2R2B gene causes autosomal dominant spinocerebellar
ataxia type 12. In the present study, we investigated the roles of CAG repeats and flanking cis elements and the associated proteins in controlling PPP2R2B expression. Deletion/site-directed mutagenesis, in silico searches
and cDNA overexpression revealed that CREB1 and SP1 bind to the conserved sequence upstream the CAG repeats to up-regulate
PPP2R2B expression, whereas TFAP4 binds to the conserved sequence downstream the CAG repeats to down-regulate PPP2R2B expression.
The binding of CREB1, SP1, and TFAP4 to the PPP2R2B promoter was further confirmed by DNA pull-down and ChIP-PCR assays. CAG
repeats itself also function as a cis element to up-regulate PPP2R2B expression as AT repeat length has no effect on PPP2R2B expression. Together, our data provide
evidence that CREB1, SP1, and TFAP4 play roles in modulating PPP2R2B expression, thus offering a mechanism of regulating PP2A
activity as the treatment of neurodegenerative diseases associated with abnormal PP2A activity. 相似文献
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Wang YC Lee CM Lee LC Tung LC Hsieh-Li HM Lee-Chen GJ Su MT 《The Journal of biological chemistry》2011,286(24):21742-21754
Spinal cerebellar ataxia type 12 (SCA12) has been attributed to the elevated expression of ppp2r2b. To better elucidate the pathomechanism of the neuronal disorder and to search for a pharmacological treatment, Drosophila models of SCA12 were generated by overexpression of a human ppp2r2b and its Drosophila homolog tws. Ectopic expression of ppp2r2b or tws caused various pathological features, including neurodegeneration, apoptosis, and shortened life span. More detailed analysis revealed that elevated ppp2r2b and tws induced fission of mitochondria accompanied by increases in cytosolic reactive oxygen species (ROS), cytochrome c, and caspase 3 activity. Transmission electron microscopy revealed that fragmented mitochondria with disrupted cristae were engulfed by autophagosomes in photoreceptor neurons of flies overexpressing tws. Additionally, transgenic flies were more susceptible to oxidative injury induced by paraquat. By contrast, ectopic Drosophila Sod2 expression and antioxidant treatment reduced ROS and caspase 3 activity and extended the life span of the SCA12 fly model. In summary, our study demonstrates that oxidative stress induced by mitochondrial dysfunction plays a causal role in SCA12, and reduction of ROS is a potential therapeutic intervention for this neuropathy. 相似文献
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