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排序方式: 共有883条查询结果,搜索用时 31 毫秒
81.
Gianni Guizzunti Thomas P. Brady Derek Fischer Vivek Malhotra Emmanuel A. Theodorakis 《Bioorganic & medicinal chemistry》2010,18(6):2115-2122
The cellular activity of norrisolide (7), a novel Golgi-vesiculating agent, was dissected as function of its chemical structure. This natural product induces irreversible vesiculation of the Golgi membranes and blocks protein transport at the level of the Golgi. The Golgi localization and fragmentation effects of 7 depend on the presence of the perhydroindane core, while the irreversibility of fragmentation depends on the acetyl group of 7. We show that fluorescent derivatives of norrisolide are able to localize to the Golgi apparatus and represent important tools for the study of the Golgi structure and function. 相似文献
82.
Ciric To Brian H. Shilton Gianni M. Di Guglielmo 《The Journal of biological chemistry》2010,285(36):27944-27957
Synthetic triterpenoids are anti-tumor agents that affect numerous cellular functions including apoptosis and growth inhibition. Here, we used mass spectrometric and protein array approaches and uncovered that triterpenoids associate with proteins of the actin cytoskeleton, including actin-related protein 3 (Arp3). Arp3, a subunit of the Arp2/3 complex, is involved in branched actin polymerization and the formation of lamellipodia. 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)-Im and CDDO-Me were observed to 1) inhibit the localization of Arp3 and actin at the leading edge of cells, 2) abrogate cell polarity, and 3) inhibit Arp2/3-dependent branched actin polymerization. We confirmed our drug effects with siRNA targeting of Arp3 and observed a decrease in Rat2 cell migration. Taken together, our data suggest that synthetic triterpenoids target Arp3 and branched actin polymerization to inhibit cell migration. 相似文献
83.
Certain chromosomal and genetic anomalies, such as Klinefelter syndrome (47,XXY) and Y chromosome microdeletions, have been
reported as potential causes of a progressive impairment of spermatogenesis. In these cases cryoconservation of ejaculated
or testicular sperm represent a valuable tool for the preservation of fertility. However, dealing with genetic disorders,
the transmission of genetic anomalies has to be taken into consideration. It is therefore important to be aware about the
clinical importance and the related genetic risks of these anomalies. In this article we describe the clinical significance
of these diseases. 相似文献
84.
Paganini S Guidetti GF Catricalà S Trionfini P Panelli S Balduini C Torti M 《Biochimie》2006,88(3-4):285-295
The Rap family of small GTP-binding proteins is composed by four different members: Rap1A, Rap1B, Rap2A and Rap2B. In this work we report the identification and characterization of a fifth member of this family of small GTPases. This new protein is highly homologous to Rap2A and Rap2B, binds labeled GTP on nitrocellulose, and is recognized by a specific anti-Rap2 antibody, but not by an anti-Rap1 antibody. The protein has thus been named Rap2C. Binding of GTP to recombinant purified Rap2C was Mg(2+)-dependent. However, accurate comparison of the kinetics of nucleotide binding and release revealed that Rap2C bound GTP less efficiently and possessed slower rate of GDP release compared to the highly homologous Rap2B. Moreover, in the presence of Mg(2+), the relative affinity of Rap2C for GTP was only about twofold higher than that for GDP, while, under the same conditions, Rap2B was able to bind GTP with about sevenfold higher affinity than GDP. When expressed in eukaryotic cells, Rap2C localized at the plasma membrane, as dictated by the presence of a CAAX motif at the C-terminus. We found that Rap2C represented the predominant Rap2 protein expressed in circulating mononuclear leukocytes, but was not present in platelets. Importantly, Rap2C was found to be expressed in human megakaryocytes, suggesting that the protein may be down-regulated during platelets generation. This work demonstrates that Rap2C is a new member of the Rap2 subfamily of proteins, able to bind guanine nucleotides with peculiar properties, and differently expressed by various hematopoietic subsets. This new protein may therefore contribute to the still poorly clarified cellular events regulated by this subfamily of GTP-binding proteins. 相似文献
85.
Oved S Mosesson Y Zwang Y Santonico E Shtiegman K Marmor MD Kochupurakkal BS Katz M Lavi S Cesareni G Yarden Y 《The Journal of biological chemistry》2006,281(31):21640-21651
When appended to the epidermal growth factor receptor (EGFR), ubiquitin serves as a sorting signal for lysosomal degradation. Here we demonstrate that the ubiquitin ligase of EGFR, namely c-Cbl, also mediates receptor modification with the ubiquitin-like molecule Nedd8. EGF stimulates receptor neddylation, which enhances subsequent ubiquitylation, as well as sorting of EGFR for degradation. Multiple lysine residues, located within the tyrosine kinase domain of EGFR, serve as attachment sites for Nedd8. A set of clathrin coat-associated binders of ubiquitin also bind Nedd8, but they undergo ubiquitylation, not neddylation. We discuss the emerging versatility of the concerted action of ubiquitylation and neddylation in the process that desensitizes growth factor-activated receptor tyrosine kinases. 相似文献
86.
Cytogenetic and molecular evaluation of centromere-associated DNA sequences from a marsupial (Macropodidae: Macropus rufogriseus) X chromosome 下载免费PDF全文
The constitution of the centromeric portions of the sex chromosomes of the red-necked wallaby, Macropus rufogriseus (family Macropodidae, subfamily Macropodinae), was investigated to develop an overview of the sequence composition of centromeres in a marsupial genome that harbors large amounts of centric and pericentric heterochromatin. The large, C-band-positive centromeric region of the X chromosome was microdissected and the isolated DNA was microcloned. Further sequence and cytogenetic analyses of three representative clones show that all chromosomes in this species carry a 178-bp satellite sequence containing a CENP-B DNA binding domain (CENP-B box) shown herein to selectively bind marsupial CENP-B protein. Two other repeats isolated in this study localize specifically to the sex chromosomes yet differ in copy number and intrachromosomal distribution. Immunocytohistochemistry assays with anti-CENP-E, anti-CREST, anti-CENP-B, and anti-trimethyl-H3K9 antibodies defined a restricted point localization of the outer kinetochore at the functional centromere within an enlarged pericentric and heterochromatic region. The distribution of these repeated sequences within the karyotype of this species, coupled with the apparent high copy number of these sequences, indicates a capacity for retention of large amounts of centromere-associated DNA in the genome of M. rufogriseus. 相似文献
87.
Using the biological species definition, yeasts of the genus Saccharomyces sensu stricto comprise six species and one natural hybrid. Previous work has shown that reproductive isolation between the species is due primarily to sequence divergence acted upon by the mismatch repair system and not due to major gene differences or chromosomal rearrangements. Sequence divergence through mismatch repair has also been shown to cause partial reproductive isolation among populations within a species. We have surveyed sequence variation in populations of Saccharomyces sensu stricto yeasts and measured meiotic sterility in hybrids. This allows us to determine the divergence necessary to produce the reproductive isolation seen among species. Rather than a sharp transition from fertility to sterility, which may have been expected, we find a smooth monotonic relationship between diversity and reproductive isolation, even as far as the well-accepted designations of S. paradoxus and S. cerevisiae as distinct species. Furthermore, we show that one species of Saccharomyces--S. cariocanus--differs from a population of S. paradoxus by four translocations, but not by sequence. There is molecular evidence of recent introgression from S. cerevisiae into the European population of S. paradoxus, supporting the idea that in nature the boundary between these species is fuzzy. 相似文献
88.
Pazzagli L Pantera B Carresi L Zoppi C Pertinhez TA Spisni A Tegli S Scala A Cappugi G 《Cell biochemistry and biophysics》2006,44(3):512-521
The ascomcete Ceratocystis fimbriata, the causal agent of “canker stain disease,” secretes a protein of 12.4 kDa that elicits phytoalexin synthesis and plant
cell death. This protein, named cerato-platanin (CP), is also located in the cell walls of ascospores, hyphae, and conidia;
it contains four cysteines (S-S bridged) and is moderately hydrophobic. The cp gene consists of a single exon and has 42 bp codifying for a signal peptide of 14 residues. The recombinant protein was obtained
by cloning the cp gene of the mature protein in Escherichia coli (BL21), and a refolding step was needed to achieve the native active form. In the European Molecular Biology data bank, CP
is reported as the first member of the CP family; this is the first example of an set of secreted fungal proteins whose primary
structure is very similar. Nonetheless, the data also revealed some structural and functional features that make CP simlar
to proteins of the hydrophobin family. 相似文献
89.
90.
The protective actions of prostacyclin (PGI(2) ) are mediated by cyclic AMP (cAMP) which is reduced by type 4 phosphodiesterases (PDE4) which hydrolyze cAMP. Superoxide (O2(-)) from NADPH oxidase (Nox) is associated with impaired PGI(2) bioactivity. The objective of this study, therefore, was to study the relationship between Nox and PDE4 expression in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with the thromboxane A(2) analog, U46619, 8-isoprostane F(2α) (8IP), or tumor necrosing factor alpha (TNFα) [±iloprost (a PGI(2) analog)] and the expression of PDE4A, B, C, and D and splice variants thereof assessed using Western blotting and qPCR and mRNA silencing of Nox4 and Nox5. Effects on cell replication and angiogenesis were also studied. U46619, 8IP, and TNFα increased the expression of Nox 4 and Nox 5 and all PDE4 isoforms as well as cell replication and tubule formation (index of angiogenesis), effects inhibited by mRNA silencing of Nox4 (but not Nox5) and iloprost and rolipram. These data demonstrate that upregulation of Nox4 leads to an upregulation of PDE4A, B, and D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis. This mechanism may be central to vasculopathies associated with endothelial dysfunction since the PGI(2)-cAMP signaling axis plays a key role in mediating functions that include hemostasis and angiogenesis. 相似文献