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11.
Procedures for isolation, from human term placenta, of highly purified nuclei and nuclear envelopes with a low content of DNA are described. Both fractions contain oestrone sulphate sulphohydrolase activity. The enzyme from nuclear envelopes can be solubilized with Triton X-100 and, partially, with proteolytic enzymes. It does not require Ca2+ and is insensitive to Ag+ and agents reacting with SH groups. It is strongly inhibited by millimolar concentrations of sulphites and to a much smaller extent by phosphates. Oxidized forms of ascorbic acid, glutathione and NAD+ revealed a pronounced inhibitory effect, whereas reduced forms of these compounds produced a slight activation. It is proposed that oestrone sulphate sulphohydrolase activity in nuclear envelopes from human placenta is not exerted by arylsulphatase but represents a specific enzyme. 相似文献
12.
Aleksandra Cegielska Godfryd Kupryszewski Alina Taylor 《Molecular & general genetics : MGG》1980,180(2):483-485
Summary Npalmitoyl-L-lysyl-L-lysine dihydrochloride ethyl ester (PLL) in sublethal doses (6–12.5 g/ml) inhibits cell division in E. coli K12 strains C600, JM1, and derivatives of JM1 carrying mutations tif-1, tif-1 sfiA, tif-1 sfiB and sfiB in conditions which do not induce SOS functions. Only sfiA mutants divide normally in the presence of PLL. This response enables direct discrimination between phenotypes of sfiA and sfiB and moreover, also the selection of spontaneous mutants sfiA in a tif
+ (recA+) genetic background. The PLL mediated inhibition of cell division in tif-1 sfiA double mutants may indicate that the recA gene product plays a role in the restoration of cell division by sfiA. 相似文献
13.
Pu Chen Justyna Aleksandra Wojdyla Ombretta Colasanti Zhijian Li Bo Qin Meitian Wang Volker Lohmann Sheng Cui 《Nucleic acids research》2022,50(16):9470
The HAV nonstructural protein 2C is essential for virus replication; however, its precise function remains elusive. Although HAV 2C shares 24–27% sequence identity with other 2Cs, key motifs are conserved. Here, we demonstrate that HAV 2C is an ATPase but lacking helicase activity. We identified an ATPase-independent nuclease activity of HAV 2C with a preference for polyuridylic single-stranded RNAs. We determined the crystal structure of an HAV 2C fragment to 2.2 Å resolution, containing an ATPase domain, a region equivalent to enterovirus 2C zinc-finger (ZFER) and a C-terminal amphipathic helix (PBD). The PBD of HAV 2C occupies a hydrophobic pocket (Pocket) in the adjacent 2C, and we show the PBD–Pocket interaction is vital for 2C functions. We identified acidic residues that are essential for the ribonuclease activity and demonstrated mutations at these sites abrogate virus replication. We built a hexameric-ring model of HAV 2C, revealing the ribonuclease-essential residues clustering around the central pore of the ring, whereas the ATPase active sites line up at the gaps between adjacent 2Cs. Finally, we show the ribonuclease activity is shared by other picornavirus 2Cs. Our findings identified a previously unfound activity of picornavirus 2C, providing novel insights into the mechanisms of virus replication. 相似文献
14.
Xu J Reumers J Couceiro JR De Smet F Gallardo R Rudyak S Cornelis A Rozenski J Zwolinska A Marine JC Lambrechts D Suh YA Rousseau F Schymkowitz J 《Nature chemical biology》2011,7(5):285-295
Many p53 missense mutations possess dominant-negative activity and oncogenic gain of function. We report that for structurally destabilized p53 mutants, these effects result from mutant-induced coaggregation of wild-type p53 and its paralogs p63 and p73, thereby also inducing a heat-shock response. Aggregation of mutant p53 resulted from self-assembly of a conserved aggregation-nucleating sequence within the hydrophobic core of the DNA-binding domain, which becomes exposed after mutation. Suppressing the aggregation propensity of this sequence by mutagenesis abrogated gain of function and restored activity of wild-type p53 and its paralogs. In the p53 germline mutation database, tumors carrying aggregation-prone p53 mutations have a significantly lower frequency of wild-type allele loss as compared to tumors harboring nonaggregating mutations, suggesting a difference in clonal selection of aggregating mutants. Overall, our study reveals a novel disease mechanism for mutant p53 gain of function and suggests that, at least in some respects, cancer could be considered an aggregation-associated disease. 相似文献
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Hjerpe R Thomas Y Chen J Zemla A Curran S Shpiro N Dick LR Kurz T 《The Biochemical journal》2012,441(3):927-936
Ubiquitin and UBL (ubiquitin-like) modifiers are small proteins that covalently modify other proteins to alter their properties or behaviours. Ubiquitin modification (ubiquitylation) targets many substrates, often leading to their proteasomal degradation. NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) is the UBL most closely related to ubiquitin, and its best-studied role is the activation of CRLs (cullin-RING ubiquitin ligases) by its conjugation to a conserved C-terminal lysine residue on cullin proteins. The attachment of UBLs requires three UBL-specific enzymes, termed E1, E2 and E3, which are usually well insulated from parallel UBL pathways. In the present study, we report a new mode of NEDD8 conjugation (NEDDylation) whereby the UBL NEDD8 is linked to proteins by ubiquitin enzymes in vivo. We found that this atypical NEDDylation is independent of classical NEDD8 enzymes, conserved from yeast to mammals, and triggered by an increase in the NEDD8 to ubiquitin ratio. In cells, NEDD8 overexpression leads to this type of NEDDylation by increasing the concentration of NEDD8, whereas proteasome inhibition has the same effect by depleting free ubiquitin. We show that bortezomib, a proteasome inhibitor used in cancer therapy, triggers atypical NEDDylation in tissue culture, which suggests that a similar process may occur in patients receiving this treatment. 相似文献
17.
Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis
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Mandic A Viktorsson K Strandberg L Heiden T Hansson J Linder S Shoshan MC 《Molecular and cellular biology》2002,22(9):3003-3013
Calpain is a ubiquitous protease with potential involvement in apoptosis. We report that in human melanoma cells, cisplatin-induced calpain activation occurs early in apoptosis. Calpain activation and subsequent apoptosis were inhibited by calpeptin and PD150606, two calpain inhibitors with different modes of action. Furthermore, cisplatin induced cleavage of the BH3-only protein Bid, yielding a 14-kDa fragment similar to proapoptotic, caspase-cleaved Bid. However, Bid cleavage was inhibited by inhibitors of calpain, but not by inhibitors of caspases or of cathepsin L. Recombinant Bid was cleaved in vitro by both recombinant calpain and by lysates of cisplatin-treated cells. Cleavage was calpeptin sensitive, and the cleavage site was mapped between Gly70 and Arg71. Calpain-cleaved Bid induced cytochrome c release from isolated mitochondria. While calpeptin did not affect cisplatin-induced modulation of Bak to its proapoptotic conformation, a dominant-negative mutant of MEKK1 (dnMEKK) inhibited Bak modulation. dnMEKK did not, however, block Bid cleavage. The combination of dnMEKK and calpeptin had an additive inhibitory effect on apoptosis. In summary, calpain-mediated Bid cleavage is important in drug-induced apoptosis, and cisplatin induces at least two separate apoptotic signaling pathways resulting in Bid cleavage and Bak modulation, respectively. 相似文献
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Aleksandra Topic Marina Milenkovic Snezana Uskokovic-Markovic Dragana Vucicevic 《Biological trace element research》2010,134(3):296-306
Investigations of effective, orally active, and safe antidiabetic metallopharmaceuticals have been carried out during the
last two decades. It has been reported that tungsten compounds mimic the action of insulin in intact cell systems. As insulin
mimetics, the most investigated tungsten compound was sodium tungstate (ST), rarely investigated was tungstophosphoric acid
(WPA), but never alanine complex of tungstophosphoric acid (WPA-A). In this study, the insulin mimetic activity of three different
tungsten compounds, ST, WPA, and WPA-A, was evaluated by means of in vitro measurements of the glucose uptake and inhibition
of free fatty acids release from epinephrine-treated isolated rat white adipocytes. We investigated the influence of concentration
(lower and higher, 0.1 and 1.0 mM, respectively) and solvent: isotonic salt solution—saline (0.9% w/v of NaCl) and dimethyl sulfoxide (DMSO; 2% v/v), on the biological effect of tested compounds. Our experimental data showed that all of the three investigated tungsten
compounds possess insulin mimetic activity in vitro on the isolated adipocytes. Influence of concentration and solvents on
insulin mimetic effect for the certain tungsten compounds were: WPA was shown effect independently of concentration and solvents;
higher concentration and DMSO were significant decreasing insulin mimetic effect of ST; lower concentration and saline led
to decreasing effect of WPA-A. Generally, there were no differences in insulin mimetic effect of three tungsten compounds
in lower concentration and dissolved in DMSO. When saline was used as solvent, it was needed higher concentration of investigated
compounds to accomplish the same effect. In conclusion, our results suggest that low concentration (0.1 mM) of ST, WPA, and
WPA-A dissolved in 2% DMSO could be the good candidates for in vivo investigation of their antidiabetic properties. 相似文献
20.