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91.
The farnesylated SNARE (N-ethylmaleimide-sensitive factor attachment protein receptor) Ykt6 mediates protein palmitoylation at the yeast vacuole by means of its amino-terminal longin domain. Ykt6 is localized equally to membranes and the cytosol, although it is unclear how this distribution is mediated. We now show that Ykt6 is released efficiently from vacuoles during an early stage of yeast vacuole fusion. This release is dependent on the disassembly of vacuolar SNAREs (priming). In recent literature, it had been demonstrated for mammalian Ykt6 that the membrane-bound form is both palmitoylated and farnesylated at its carboxy-terminal CAAX box, whereas soluble Ykt6 is only farnesylated. In agreement with this, we find that yeast Ykt6 becomes palmitoylated in vitro at its C-terminal CAAX motif. Mutagenesis of the potential palmitoylation site in yeast Ykt6 prevents stable membrane association and is lethal. On the basis of these and other findings, we speculate that Ykt6 is released from membranes by depalmitoylation. Such a mechanism could enable recycling of this lipid-anchored SNARE from the vacuole independent of retrograde transport. 相似文献
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Karolina Lindberg Anders Ström John G. Lock Jan‐Åke Gustafsson Lars‐Arne Haldosén Luisa A. Helguero 《Journal of cellular physiology》2010,222(1):156-167
Estrogen effects on mammary gland development and differentiation are mediated by two receptors (ERα and ERβ). Estrogen‐bound ERα induces proliferation of mammary epithelial and cancer cells, while ERβ is important for maintenance of the differentiated epithelium and inhibits proliferation in different cell systems. In addition, the normal breast contains higher ERβ levels compared to the early stage breast cancers, suggesting that loss of ERβ could be important in cancer development. Analysis of ERβ?/? mice has consistently revealed reduced expression of cell adhesion proteins. As such, ERβ is a candidate modulator of epithelial homeostasis and metastasis. Consequently, the aim of this study was to analyze estrogenic effects on adhesion of breast cancer cells expressing ERα and ERβ. As ERβ is widely found in breast cancer but not in cell lines, we used ERα positive T47‐D and MCF‐7 human breast cancer cells to generate cells with inducible ERβ expression. Furthermore, the colon cancer cell lines SW480 and HT‐29 were also used. Integrin α1 mRNA and protein levels increased following ERβ expression. Integrin β1—the unique partner for integrin α1—increased only at the protein level. ERβ expression enhanced the formation of vinculin containing focal complexes and actin filaments, indicating a more adhesive potential. This was confirmed by adhesion assays where ERβ increased adhesion to different extracellular matrix proteins, mostly laminin. In addition, ERβ expression was associated to less cell migration. These results indicate that ERβ affects integrin expression and clustering and consequently modulates adhesion and migration of breast cancer cells. J. Cell. Physiol. 222:156–167, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
94.
Cruz MN Luksha L Logman H Poston L Agewall S Kublickiene K 《American journal of physiology. Heart and circulatory physiology》2006,290(5):H1969-H1975
The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ERalpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERbeta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERalpha agonist) were determined. These were compared with responses to reference compound 17beta-estradiol (17beta-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17beta-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17beta-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD. 相似文献
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Ma?gorzata Sowiak Karolina Bródka Alina Buczyńska Marcin Cyprowski Anna Kozajda Wojciech Sobala Irena Szadkowska-Stańczyk 《Aerobiologia》2012,28(2):121-133
The project was aimed at evaluating the potential occupational exposure of swine farm workers to dust and microorganisms present
in piggery bioaerosols (especially in its respirable fraction) under various breeding conditions. Sampling was carried out
in 14 buildings located at 13 pig breeding and production farms in Poland. Concentrations of inhalable and respirable dusts
in the air of the piggeries were low (means, respectively, 1.76 and 0.23 mg/m3). The concentration of microorganisms was generally high (mean = 3.53 × 105 cfu/m3). More than 96% of determined microorganisms were bacteria (mean = 3.42 × 105 cfu/m3). The fungal concentration was distinctly lower (mean = 2.71 × 103 cfu/m3). The concentration of bacteria in the respirable fraction of bioaerosol (mean = 1.51 × 105 cfu/m3) made up for 48.2% of their total concentration, while the level of fungi in that fraction (mean = 1.50 × 103 cfu/m3) formed 68.8% of the total fungal concentration. The concentration of inhalable dust was significantly modified by the type
of breeding system. The factors that significantly affected the total concentrations of microbes and bacteria, as well as
their levels in the bioaerosols’ respirable fraction were as follows: herd size, breeding system, feeding method and the type
of ventilation system. In the case of fungi, these were the livestock breeding system and the feeding method. Moreover, there
was a high positive correlation of inhalable dust concentrations with the fungal concentration, CO2 and relative humidity. A negative correlation was found between concentrations of each microbe group and the airflow velocity.
Swine farm workers are exposed to relatively low dust concentrations and high concentrations of microorganisms, bacteria in
particular. Fungi, to a much larger extent than bacteria, are correlated with the respirable particles of a piggery bioaerosol,
which may harm the respiratory system of exposed workers. 相似文献
98.
99.
Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response 总被引:1,自引:0,他引:1
McKibbin C Mares A Piacenti M Williams H Roboti P Puumalainen M Callan AC Lesiak-Mieczkowska K Linder S Harant H High S Flitsch SL Whitehead RC Swanton E 《The Biochemical journal》2012,442(3):639-648
Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ES(I) (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ES(I) causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel mechanism that contributes to UPR activation. 相似文献
100.
Rahman KM Tizkova K Reszka AP Neidle S Thurston DE 《Bioorganic & medicinal chemistry letters》2012,22(8):3006-3010
Thirteen compounds with diverse chemical structures have been identified as selective telomeric G-quadruplex-binding ligands through screening the NCI Diversity Set II, the NCI Natural Products Set II and the NCI Mechanistic Diversity Set libraries containing a total of 2307 members against a human telomeric G-quadruplex using a FRET-based DNA melting assay. These compounds show significant selectivity towards a telomeric G-quadruplex compared to duplex DNA, fall within a molecular weight range of 327-533, and are generally consistent with the Lipinski Rule of Five for drug-likeness. Thus they provide new chemical scaffolds for the development of novel classes of G-quadruplex-targeting agents. 相似文献