共查询到20条相似文献,搜索用时 15 毫秒
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Cohen RN Putney A Wondisford FE Hollenberg AN 《Molecular endocrinology (Baltimore, Md.)》2000,14(6):900-914
The thyroid hormone receptor (TR) and retinoic acid receptor (RAR) isoforms have the capacity to silence gene expression in the absence of their ligands on target response elements. This active repression is mediated by the ability of the corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), to recruit a complex containing histone deacetylase activity. Interestingly, NCoR and SMRT share significant differences in the their two nuclear receptor-interacting domains (IDs), suggesting that they may recruit receptors with different affinities. In addition, the role of the receptor complex bound to a response element has not been fully evaluated in its ability to recruit separate corepressors. We demonstrate in this report that the proximal ID in NCoR and SMRT, which share only 23% homology, allows preferential recognition of nuclear receptors, such that TR prefers to recruit NCoR, and RAR prefers to recruit SMRT, to DNA response elements. However, mutations in the TR found in the syndromes of resistance to thyroid hormone can change the corepressor recruited by changing the complex (homodimer or heterodimer) formed on the TRE. These results demonstrate that the corepressor complex recruited can be both nuclear receptor- and receptor complex-specific. 相似文献
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Makowski A Brzostek S Cohen RN Hollenberg AN 《Molecular endocrinology (Baltimore, Md.)》2003,17(2):273-286
The thyroid hormone receptor (TR) recruits the nuclear corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), to target DNA elements in the absence of ligand. While the TR preferentially recruits NCoR, the mechanism remains unclear. The corepressors interact with the TR via interacting domains (IDs) present in their C terminus which contain a conserved motif termed a CoRNR box. Despite their similarity, the corepressor IDs allow for nuclear receptor specificity. Here we demonstrate that NCoR stabilizes the TR homodimer when bound to DNA by preventing its dissociation from thyroid hormone response elements. This suggests that NCoR acts to hold the repression complex in place on target elements. The TR homodimer recruits NCoR through two of its three IDs, one of which is not present in SMRT. This unique ID, N3, contains a CoRNR box but lacks the extended helical motif present in each of the other IDs. Instead, N3 contains an isoleucine just proximal to this motif. This isoleucine is also conserved in N2 but not in the corresponding S2 domain in SMRT. On thyroid hormone response elements and in mammalian cells this residue is critical in both N3 and N2 for high-affinity TR binding. In addition, this residue also controls specificity for the interactions of TR with NCoR. Together these data suggest that the specific recruitment of NCoR by the TR through a unique motif allows for stabilization of the repression complex on target elements. 相似文献
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Yao-Hsuan Tseng Der-Shan Sun Wen-Shiang Wu Hao Chan Ming-Syuan Syue Han-Chen Ho Hsin-Hou Chang 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Traditional antibacterial photocatalysts are primarily induced by ultraviolet light to elicit antibacterial reactive oxygen species. New generation visible-light responsive photocatalysts were discovered, offering greater opportunity to use photocatalysts as disinfectants in our living environment. Recently, we found that visible-light responsive platinum-containing titania (TiO2–Pt) exerted high performance antibacterial property against soil-borne pathogens even in soil highly contaminated water. However, its physical and photocatalytic properties, and the application in vivo have not been well-characterized.Methods
Transmission electron microscopy, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, ultraviolet–visible absorption spectrum and the removal rate of nitrogen oxides were therefore analyzed. The antibacterial performance under in vitro and in vivo conditions was evaluated.Results
The apparent quantum efficiency for visible light illuminated TiO2–Pt is relatively higher than several other titania photocatalysts. The killing effect achieved approximately 2 log reductions of pathogenic bacteria in vitro. Illumination of injected TiO2–Pt successfully ameliorated the subcutaneous infection in mice.Conclusions
This is the first demonstration of in vivo antibacterial use of TiO2–Pt nanoparticles. When compared to nanoparticles of some other visible-light responsive photocatalysts, TiO2–Pt nanoparticles induced less adverse effects such as exacerbated platelet clearance and hepatic cytotoxicity in vivo.General significance
These findings suggest that the TiO2–Pt may have potential application on the development of an antibacterial material in both in vitro and in vivo settings. 相似文献11.
Ana Paula Zanatta Leila Zanatta Renata Gonçalves Ariane Zamoner Fátima Regina Mena Barreto Silva 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
The secretory activity of Sertoli cells (SC) is dependent on ion channel functions and protein synthesis and is critical to ongoing spermatogenesis. The aim of this study was to investigate the mechanism of action associated with a non-metabolizable amino acid [14C]-MeAIB (α-(methyl-amino)isobutyric acid) accumulation stimulated by T4 and the role of the integrin receptor in this event, and also to clarify whether the T4 effect on MeAIB accumulation and on Ca2+ influx culminates in cell secretion.Methods
We have studied the rapid and plasma membrane initiated effects of T4 by using 45Ca2+ uptake and [45C]-MeAIB accumulation assays, respectively. Thymidine incorporation into DNA was used to monitor nuclear activity and quinacrine to analyze the secretory activity on SC.Results
The stimulation of MeAIB accumulation by T4 appears to be mediated by the integrin receptor in the plasma membrane since tetrac and RGD peptide were able to nullify the effect of this hormone. In addition, T4 increases extracellular Ca2+ uptake and Ca2+ from intracellular stocks to enhance nuclear activity, but this genomic action seems not to influence SC secretion mediated by T4. Also, the cytoskeleton and ClC-3 chloride channel contribute to the membrane-associated responses of SC.Conclusions
T4 integrin receptor activation ultimately determines the plasma membrane responses on amino acid transport in SC, but it is not involved in calcium influx, cell secretion or the nuclear effect of the hormone.General significance
The integrin receptor activation by T4 may take a role in plasma membrane processes involved in the male reproductive system. 相似文献12.
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The Bcl-2 associated athanogene 1M (Bag-1M) is known to repress the transactivation of the glucocorticoid receptor (GR). We report here that Bag-1M inhibits the action of GR via recruitment of corepressors, including nuclear receptor corepressor (NcoR) and silencing mediator for retinoic acid and thyroid hormone receptor (SMRT), and histone deacetylase (HDAC)3 to the genomic response element of a glucocorticoid-regulated human metallothionein IIa (hMTIIa) gene. A mutant GR lacking the interaction with BAG-1M fails to recruit the corepressors NcoR and SMRT. RNAi-mediated knock down of corepressors and the use of HDAC inhibitor relieved Bag-1M-induced repression on the transactivation of the GR. In addition, Bag-1M is not involved in the degradation of the receptor. These findings indicate a novel mechanism by which Bag-1M acts as a corepressor and downregulates the activity of the GR.
Structured summary
MINT-7216164: HDAC3 (uniprotkb:O15379) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)MINT-7216183: NCOR (uniprotkb:O75376) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)MINT-7216175: SMRT (uniprotkb:Q9Y618) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006) 相似文献18.
Nadia Schoenmakers Carla Moran Robin P. Peeters Theo Visser Mark Gurnell Krishna Chatterjee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Thyroid hormone acts via receptor subtypes (TRα1, TRβ1, TRβ2) with differing tissue distributions, encoded by distinct genes (THRA, THRB). THRB mutations cause a disorder with central (hypothalamic–pituitary) resistance to thyroid hormone action with markedly elevated thyroid hormone and normal TSH levels.Scope of review
This review describes the clinical features, genetic and molecular pathogenesis of a homologous human disorder mediated by defective THRA. Clinical features include growth retardation, skeletal dysplasia and constipation associated with low-normal T4 and high-normal T3 levels and a low T4/T3 ratio, together with subnormal reverse T3 levels. Heterozygous TRa1 mutations in affected individuals generate defective mutant receptors which inhibit wild-type receptor action in a dominant negative manner.Major conclusions
Mutations in human TRα1 mediate RTH with features of hypothyroidism in particular tissues (e.g. skeleton, gastrointestinal tract), but are not associated with a markedly dysregulated pituitary–thyroid axis.General significance
Human THRA mutations could be more common but may have eluded discovery due to the absence of overt thyroid dysfunction. Nevertheless, in the appropriate clinical context, a thyroid biochemical signature (low T4/T3 ratio, subnormal reverse T3 levels), may enable future identification of cases.This article is part of a Special Issue entitled Thyroid hormone signalling. 相似文献19.
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Xinni Xie Xinbo Zhou Wei Chen Long Long Wei Li Xiuyan Yang Song Li Lili Wang 《Biochimica et Biophysica Acta (BBA)/General Subjects》2015