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991.
992.
Sultan A Nesslany F Violet M Bégard S Loyens A Talahari S Mansuroglu Z Marzin D Sergeant N Humez S Colin M Bonnefoy E Buée L Galas MC 《The Journal of biological chemistry》2011,286(6):4566-4575
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute oxidative stress and mild heat stress (HS) induce the accumulation of dephosphorylated Tau in neuronal nuclei. Using chromatin immunoprecipitation assays, we demonstrate that the capacity of endogenous Tau to interact with neuronal DNA increased following HS. Comet assays performed on both wild-type and Tau-deficient neuronal cultures showed that Tau fully protected neuronal genomic DNA against HS-induced damage. Interestingly, HS-induced DNA damage observed in Tau-deficient cells was completely rescued after the overexpression of human Tau targeted to the nucleus. These results highlight a novel role for nuclear Tau as a key player in early stress response. 相似文献
993.
Roux F Colomé-Tatché M Edelist C Wardenaar R Guerche P Hospital F Colot V Jansen RC Johannes F 《Genetics》2011,188(4):1015-1017
We extensively phenotyped 6000 Arabidopsis plants with experimentally perturbed DNA methylomes as well as a diverse panel of natural accessions in a common garden. We found that alterations in DNA methylation not only caused heritable phenotypic diversity but also produced heritability patterns closely resembling those of the natural accessions. Our findings indicate that epigenetically induced and naturally occurring variation in complex traits share part of their polygenic architecture and may offer complementary adaptation routes in ecological settings. 相似文献
994.
995.
996.
Amphipols (APols) are amphiphatic polymers that keep membrane proteins (MPs) water-soluble. The best characterized and most widely used APol to date, A8-35, comprises a polyacrylate backbone grafted with octyl- and isopropylamine side chains. The nature of its hydrophilic moieties prevents its use at the slightly acidic pH that is desirable to slow down the rate of amide proton exchange in solution NMR studies. We describe here the synthesis and properties of pH-insensitive APols obtained by replacing isopropyles with taurine. Sulfonated APols (SAPols) can be used to trap MPs in the form of small complexes, to stabilize them, and to keep them water-soluble even at low pH. [(15) N,(1) H]-transverse relaxation-optimized spectroscopy NMR spectra obtained at pH 6.8 of a bacterial outer MP folded in SAPols show that the protein is correctly folded. The spectra have a resolution similar to that achieved with A8-35 and reveal water-exposed amide and indole protons whose resonance peaks are absent at pH 8.0. 相似文献
997.
Cytokines tumor necrosis factor-α and interferon-γ induce pancreatic β-cell apoptosis through STAT1-mediated Bim protein activation 总被引:1,自引:0,他引:1
998.
Jrad-Lamine A Henry-Berger J Gourbeyre P Damon-Soubeyrand C Lenoir A Combaret L Saez F Kocer A Tone S Fuchs D Zhu W Oefner PJ Munn DH Mellor AL Gharbi N Cadet R Aitken RJ Drevet JR 《The Journal of biological chemistry》2011,286(10):8030-8042
Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1(-/-)-deficient mice. In the caput epididymis of Ido1(-/-) animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal. 相似文献
999.
Levaot N Voytyuk O Dimitriou I Sircoulomb F Chandrakumar A Deckert M Krzyzanowski PM Scotter A Gu S Janmohamed S Cong F Simoncic PD Ueki Y La Rose J Rottapel R 《Cell》2011,147(6):1324-1339
Cherubism is an autosomal-dominant syndrome characterized by inflammatory destructive bony lesions resulting in symmetrical deformities of the facial bones. Cherubism is caused by mutations in Sh3bp2, the gene that encodes the adaptor protein 3BP2. Most identified mutations in 3BP2 lie within the peptide sequence RSPPDG. A mouse model of cherubism develops hyperactive bone-remodeling osteoclasts and systemic inflammation characterized by expansion of the myelomonocytic lineage. The mechanism by which cherubism mutations alter 3BP2 function has remained obscure. Here we show that Tankyrase, a member of the poly(ADP-ribose)polymerase (PARP) family, regulates 3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the SRC, SYK, and VAV signaling pathways. 相似文献
1000.
As a result of an intense host-parasite evolutionary arms race, parasitic wasps frequently display high levels of specialization on very few host species. For instance, in braconid wasps very few generalist species have been described. However, within this family, Cotesia sesamiae is a generalist species that is widespread in sub-Saharan Africa and develops on several lepidopteran hosts. In this study, we tested the hypothesis that C.?sesamiae may be a cryptic specialist when examined at the intraspecific level. We sequenced exon 2 of CrV1, a gene of the symbiotic polyDNAvirus that is integrated into the wasp genome and is associated with host immune suppression. We found that CrV1 genotype was more closely associated with the host in which the parasitoid developed than any abiotic environmental factor tested. We also tested a correlation between CrV1 genotype and an infection with Wolbachia bacteria, which are known for their ability to induce reproductive isolation. The Wolbachia bacteria infection polymorphism was also found as a major factor explaining the genetic structure of CrV1, and, in addition, the best model explaining CrV1 genetic structure involved an interaction between Wolbachia infection and host species. We suggest that Wolbachia could act as an agent capable of maintaining advantageous alleles for host specialization in different populations of C.?sesamiae. This mechanism could be applicable to other insect models because of the high prevalence of Wolbachia in insects. 相似文献