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221.
Xaf1 can cooperate with TNFα in the induction of apoptosis, independently of interaction with XIAP 总被引:5,自引:0,他引:5
Xia Y Novak R Lewis J Duckett CS Phillips AC 《Molecular and cellular biochemistry》2006,286(1-2):67-76
XIAP-associated factor 1 (Xaf1) binds XIAP and re-localizes it to the nucleus, thus inhibiting XIAP activity and enhancing apoptosis [1]. Xaf1 expression is reduced or absent in tumor samples and cell lines suggesting it may function as a tumor suppressor [2–5]. To further study Xaf1 function we generated Xaf1 inducible cells in the osteosarcoma cell line Saos-2. Despite Xaf1 inducing apoptosis that is dramatically enhanced by TNFα we find no evidence for an interaction between Xaf1 and XIAP. Furthermore, Xaf1 expression sensitized XIAP−/− fibroblasts to TNFα, demonstrating the existence of a novel mechanism of Xaf1 induced apoptosis distinct from antagonizing XIAP. Xaf1 expression promotes cytochrome c release that cannot be blocked by inhibition of caspase activity. This implicates a role for the mitochondrial apoptotic pathway, consistent with the ability of Bcl2 to block Xaf1 induced apoptosis. The data indicate that in Saos2 cells Xaf1 activates the mitochondrial apoptotic pathway to facilitate cytochrome c release, thus amplifying apoptotic signals from death receptors. 相似文献
222.
Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins 总被引:8,自引:0,他引:8
Creagh EM Murphy BM Duriez PJ Duckett CS Martin SJ 《The Journal of biological chemistry》2004,279(26):26906-26914
Inhibitor of apoptosis proteins (IAPs) can block apoptosis through binding to active caspases and antagonizing their function. IAP function can be neutralized by Smac/Diablo, an IAP-binding protein that is released from mitochondria during apoptosis. In addition to their ability to interact with caspases, certain IAPs also display ubiquitin-protein isopeptide ligase activity because of the presence of a RING domain. However, it is not known whether the ubiquitin-protein isopeptide ligase activities of human IAPs contribute to their apoptosis inhibitory activity or whether this IAP property can be modulated through association with Smac/Diablo. Here we demonstrate that the ubiquitin ligase activities of XIAP, and to a lesser extent c-IAP-1 and c-IAP2, are potently repressed through binding to Smac/Diablo. We also show that mutation of the XIAP RING domain rendered this IAP a less effective inhibitor of apoptosis, suggesting that the ubiquitin ligase activity of XIAP contributes to its anti-apoptotic function. These data suggest that Smac/Diablo potentiates apoptosis by simultaneously antagonizing caspase-IAP interactions and repressing IAP ubiquitin ligase activities. 相似文献
223.
Bin Jiang Jeffrey Mason Anahid Jewett William CS Cho Yan-gao Man 《International journal of biological sciences》2012,8(8):1206-1216
Background: A great number of in vitro and in vivo studies have suggested that many pathways or factors can stimulate angiogenesis and lymphangiogenesis, which facilitate tumor progression and metastasis. However, the morphological and immunohistochemical profile of newly formed vasculatures has not been elucidated, making it difficult to differentiate them from the pre-existing ones, and to identify their unique molecular profiles for diagnosis and therapeutic interventions.Experimental findings: As cytokeratin (CK)-19 is a well-recognized stem cell marker and CK-19-positive cells are frequently detected in the peripheral blood of patients with metastatic cancer, our recent studies have assessed the involvement of CK-19 in the formation of new vasculatures in primary colorectal cancer (CRC) tissues. Our studies showed that a subset of lymph node-positive cases harbored some isolated normal epithelial structures with distinct CK-19 immunostaining within an otherwise CK-19-negative background. These structures are exclusively located within or adjacent to lymphoid follicles and are often surrounded by tube-like structures expressing lymphatic endothelial marker D2-40. Similar structures are more frequently seen at the junctions between pre-invasive and invasive CRC with the following features: (1). they consist of a single layer of endothelial cells that express both D2-40 and CD34, (2). their endothelial walls are often incomplete with disseminated cells protruding into the adjacent stroma, and (3). they are exclusively associated with disseminated CK-19-positive cellsHypothesis: Based on these findings, we propose that these tube-like structures represent newly formed vasculatures, which are derived by the convergence of aberrant lymphocyte infiltration and tumor stem cells. Because of their close physical proximity, tumor stem cells within the epithelial and stromal components contribute equally and coordinately to the morphogenesis of new vasculatures, which constitutes the basis for the unique morphologic and immunohistochemical features of newly formed vasculatures. Our hypothesis appears to be applicable to all epithelium-derived cancers. 相似文献
224.
We measured serum dehydroepiandrosterone sulfate (DHEA-S) levels by nine different radioimmunoassay (RIA) methods. Although each method was adequate for determining the amount of authentic DHEA-S, there were marked differences observed between the methods when serum samples were tested. Further, the pattern of these differences varied in different clinical situations. We suggest that the differences in the apparent DHEA-S content resulted from the presence of structurally related compounds which differ in their cross-reactivity in the different RIAs. One of these cross-reacting materials may be a functional androgen. 相似文献
225.
Comparative ultrastructural observations reveal that cytoplasmic deletion during spermatogenesis in Sphagnum and other mosses (Bryopsida) has two distinct phases. In young spermatids, Golgi-derived vesicles produce the mucopolysaccharide sheaths in which the gametes are liberated. Golgi bodies, however, play no part in removal of cytoplasm during gamete maturation. Rounding off of the cells during this process results in a 50% reduction in volume. Mid-spermatid stages in Sphagnum are characterised by the sequential loss of Golgi bodies and endoplasmic reticulum (ER) but no further diminution of the cytoplasm. The final stages of nuclear metamorphosis and chromatin condensation, in late spermatids, are marked by the sudden appearance, in the otherwise featureless central cytoplasm, of a membrane vesicle complex (MVC) comprising cisternae, tubules, and smooth and coated vesicles. Following repositioning of the MVC beneath the plasma membrane, rapid shrinkage of the cytoplasm is associated with the presence of vesicle fusion profiles at the cell surface. The MVC is considered to be intimately involved in cytoplasmic breakdown and loss. Acid phosphatase activity can be detected throughout spermatogenesis. Spermatogenous cells and young spermatids possess relatively low levels of the enzyme, restricted to the ER and perinuclear space, but particularly high levels occur in the MVC region of late spermatids of Sphagnum. The deletion process in Bryopsida is much more gradual than that of Sphagnum. Mid-spermatids contain sheets of ER, Golgi with small vesicles, and irregular cisternae associated with coated vesicles. Vacuoles derived either from dilation of the ER or the coated vesicle complexes gradually increase in size and number at the expense of the cytoplasm. During the early stages of chromatin condensation, a large central vacuole opens onto the anterior face of the gametes. Further discharge of vesicles continues throughout gamete maturation. A comparative survey of spermatogenesis in land plants indicates that cytoplasmic deletion is achieved in different ways in different groups. We speculate that the spermatozoids of the common ancestor of archegoniate plants probably possessed large amounts of cytoplasm. The deletion mechanisms may have originated from a contractile vacuole apparatus. 相似文献
226.
Summary Post-meiotic tetraspore mother cells of Corallina officinalis L. have been studied by light and electron microscopy. During the course of post-meiotic cellular reorganisation each nucleus becomes surrounded by a complex of precisely oriented endoplasmic reticulum, termed nuclear endoplasmic reticulum. A distinctive feature of this relationship is an electron dense substance in contact with the nuclear surface and extending as groundplasm between the ER cisternae as far as the outer limits of the complex, where it gives place to the ribosome-containing matrix of the general cytoplasm. There is circumstantial evidence to indicate that the extracisternal electron dense material is a product of nucleo-cytoplasmic interaction, and that it is involved in the assembly of ribosomes.The nuclear endoplasmic reticulum appears to be active in the production of smaller swollen cisternal elements, which form frequently anastomosing reticular tracts in the regions between adjacent nuclei. There is structural evidence of vesicular transport of material from the swollen cisternae to the proximal (forming) face of the Golgi apparatus.These events are thought to be of fundamental importance in achieving the cellular reorganisation and transformation which occurs after the second meiotic division.The authors thank Mr. D. C. Williams for technical assistance. One of us (MCP) gratefully acknowledges the financial support provided by a Natural Environment Research Council Studentship. 相似文献
227.
The inhibitory effect of 23N-alkyl-4-piperidylesters (alkyl = ethyl-butyl) (APEA) and 8N-ethyl-2-pyrrolidinylmethylesters (EPMEA) of 2- and 3-substituted alkoxyphenylcarbamic acids (alkoxy = butoxy-heptyloxy-) on photosynthetic Hill reaction activity of spinach chloroplasts and on chlorophyll (Chl) synthesis in green algaeChlorella vulgaris was investigated. Inhibitory activities of these compounds were strongly connected with the lipophilicity of the whole molecule. A lower inhibitory activity of 2-alkoxy-substituted derivatives in relation to the corresponding 3-substituted ones was confirmed. Electron spin resonance (ESR) spectra of spinach chloroplasts demonstrated that the studied compounds affected the structure of photosystem (PS) 2 with the release of Mn2+ ions into interior of thylakoid membranes. 相似文献
228.
Douglas E. Coplen Pamela S. Howard John W. Duckett Howard M. Snyder Edward J. Macarak 《In vitro cellular & developmental biology. Animal》1994,30(9):604-608
Summary For the first time we report on the growth, culture, and matrix production characteristics of a cell type isolated from the
lamina propria of the urinary bladder wall. A fibroblastlike cell was identified as distinct from bladder detrusor smooth
muscle cells and urothelium based on morphology, growth characteristics, and immunohistochemical staining. Characterization
of extracellular matrix synthesis by this cell type using35S-methionine metabolic labeling demonstrated that these cells are capable of secreting components of the surrounding connective
tissue, including several fibrillar collagens, a basement membrane collagen, and fibronectin. 相似文献
229.
K.J. Oparka C.M. Duckett D.A.M. Prior D.B. Fisher 《The Plant journal : for cell and molecular biology》1994,6(5):759-766
Confocal laser scanning microscopy (CLSM) has been used to image phloem transport and unloading in the root tip of Arabidopsis. The fluorescent probe 5(6) carboxyfluorescein (CF) was ester loaded into a single cotyledon and the entire seedling placed within an observation chamber under the microscope. Translocation of CF to the root tip was rapid, followed by unloading into discrete concentric files of cells. The position of the prominent unloading ‘zone’ corresponded precisely with that of the two protophloem files of sieve elements, demonstrating a functional role of these cells in symplastic sieve-element unloading. Symplastic transport following unloading was confined to the elongating zone of the root with little basipetal transport to more mature cells. Following photobleaching of the unloading zone, phloem transport was restored immediately into the protophloem sieve elements, followed rapidly by lateral, symplastic sieve-element unloading. The results demonstrate that phloem transport processes can now be imaged in real time, and non-invasively, within an intact plant system. 相似文献
230.
XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome and prevents CD95- and Bax-induced apoptosis 总被引:7,自引:0,他引:7
Bratton SB Lewis J Butterworth M Duckett CS Cohen GM 《Cell death and differentiation》2002,9(9):881-892
Ligation of death receptors or formation of the Apaf-1 apoptosome results in the activation of caspases and execution of apoptosis. We recently demonstrated that X-linked inhibitor-of-apoptosis protein (XIAP) associates with the apoptosome in vitro. By utilizing XIAP mutants, we now report that XIAP binds to the 'native' apoptosome complex via a specific interaction with the small p12 subunit of processed caspase-9. Indeed, we provide the first direct evidence that XIAP can simultaneously bind active caspases-9 and -3 within the same complex and that inhibition of caspase-3 by the Linker-BIR2 domain prevents disruption of BIR3-caspase-9 interactions. Recent studies suggest that inhibition of caspase-3 is dispensable for its anti-apoptotic effects. However, we clearly demonstrate that inhibition of caspase-3 is required to inhibit CD95 (Fas/Apo-1)-mediated apoptosis, whereas inhibition of either caspase-9 or caspase-3 prevents Bax-induced cell death. Finally, we illustrate for the first time that XIAP mutants, which are incapable of binding to caspases-9 and -3 are completely devoid of anti-apoptotic activity. Thus, XIAP's capacity to maintain inhibition of caspase-9 within the Apaf-1 apoptosome is influenced by its ability to simultaneously inhibit active caspase-3, and depending upon the apoptotic stimulus, inhibition of caspase-9 or 3 is essential for XIAP's anti-apoptotic activity. 相似文献