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101.
PIWIL2, called HILI in humans, is a member of the PIWI subfamily. This subfamily has highly conserved PAZ and Piwi domains and is implicated in several critical functions, including embryonic development, stem-cell self-renewal, RNA silencing, and translational control. However, the underlying molecular mechanism remains largely unknown. Transforming growth factor-β (TGF-β) is a secreted multifunctional protein that controls several developmental processes and the pathogenesis of many diseases. TGF-β signaling is activated by phosphorylation of transmembrane serine/threonine kinase receptors, TGF-β type II (TβRII), and type I (TβRI), which are stabilized by Hsp90 via specific interactions with this molecular chaperone. Here, we present evidence that HILI suppresses TGF-β signaling by physically associating with Hsp90 in human embryonic kidney cells (HEK-293). Our research shows that HILI mediates the loss of TGF-β-induced Smad2/3 phosphorylation. We also demonstrate that HILI interacts with Hsp90 to prevent formation of Hsp90-TβR heteromeric complexes, and improves ubiquitination and degradation of TβRs dependent on the ubiquitin E3 ligase Smurf2. This work reveals a critical negative regulation level of TGF-β signaling mediated by HILI (human PIWIL2) by its ability to interact with Hsp90 and promote TβR degradation. 相似文献
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Dragon's blood may have radioprotective effects in radiation-induced rat brain injury 总被引:2,自引:0,他引:2
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An Allele-specific PCR Assay for Detecting Azoxystrobin-resistant Alternaria Isolates from Pistachio in California 总被引:1,自引:0,他引:1
Alternaria late blight caused by Alternaria spp. in the alternata, tenuissima and arborescens species‐groups is one of the most common fungal diseases of pistachio in California. A single point mutation resulting in the replacement of a glycine by an alanine at codon 143 (G143A) in the mitochondrial cytochrome b (cyt b) has been found in all azoxystrobin‐resistant isolates of these three species from California pistachio. In this study, a pair of allele‐specific polymerase chain reaction (PCR) primers was developed to detect this point mutation. The allele‐specific PCR assay coupled with a rapid DNA extraction method could detect azoxystrobin‐resistant Alternaria isolates in a few hours. The allele‐specific PCR method was also reliable for detecting azoxystrobin‐resistant Alternaria directly in both laboratory‐inoculated and naturally infected pistachio leaves. 相似文献
106.
Bovine and human insulin activate CD8+-autoreactive CTL expressing both type 1 and type 2 cytokines in C57BL/6 mice 总被引:2,自引:0,他引:2
CD8+ T cells down-regulate a variety of immune responses. For example, porcine and human insulin do not stimulate Abs in C57BL/6 mice because CD8+ T cells inhibit CD4+ helper T cells. By contrast, bovine insulin induces Ab in C57BL/6 mice, and removal of CD8+ T cells does not alter this response. This raises the question of whether porcine, but not bovine, insulin activates CD8+ T cells or whether both insulins activate CD8+ T cells but CD4+ helper T cells are differentially inhibited by them. In this study, we show that insulin-specific CD8+ CTL can be cultured from C57BL/6 mice primed with either bovine or human insulin in CFA. Thus, exogenous Ags, besides OVA, induce CD8+ CTL when administered in an adjuvant, suggesting this is a typical response. These CTL are H-2Kb restricted and produce IL-5, IL-10, IFN-gamma, and small amounts of IL-4, which is distinct from IFN-gamma and TNF-alpha that are typically secreted by virus-specific CTL. Moreover, the CTL primed with either bovine or human insulin recognize an A-chain peptide that is identical to the mouse insulin sequence. That foreign proteins, which are closely related to self-proteins, activated autoreactive, CD8+ T cells in vivo is a novel finding. It raises the possibility that self-reactive CTL may be activated by cross-reacting Ags and once activated they might participate in autoimmunity. These results also suggest that down-regulation of insulin-specific responses by autoreactive CD8+ T cells is most likely due to the differential sensitivity of bovine and human insulin-specific CD4+ T cells. 相似文献
107.
Guan S Ma S Zhu Y Ge R Wang Q Wang JH 《Biochemical and biophysical research communications》2006,345(1):175-180
Cerebellum is involved in the motion coordination and working memory, to which the programming of sequential spikes at Purkinje cells is essential. It is not clear about the intrinsic mechanisms underlying spike capacity and timing precision as well as their postnatal maturation. We investigated the programming and intrinsic property of sequential spikes at Purkinje neurons during postnatal development by whole-cell recording in cerebellar slices. Cerebellar Purkinje neurons demonstrate the increasing of spike capacity and timing precision, as well as the lowering of refractory periods and threshold potentials during the postnatal maturation. In addition, the correlation between spike parameters and intrinsic properties converts to be more linear. This postnatal plasticity of neuronal intrinsic properties improves the timing precision and capacity of spike programming at cerebellar Purkinje neurons. 相似文献
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Olivia Sveidahl Johansen Tao Ma Jakob Bondo Hansen Lasse Kruse Markussen Renate Schreiber Laia Reverte-Salisa Hua Dong Dan Ploug Christensen Wenfei Sun Thorsten Gnad Iuliia Karavaeva Thomas Svava Nielsen Sander Kooijman Cheryl Cero Oksana Dmytriyeva Yachen Shen Maria Razzoli Shannon L. O’Brien Zachary Gerhart-Hines 《Cell》2021,184(13):3502-3518.e33