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The p53 pathway and apoptosis. 总被引:17,自引:0,他引:17
4.
The effects of various anionic phospholipids on the in vitro assembly of MAP2/tubulin microtubules has been examined. We show that the potency to inhibit is related to the polarity of the phospholipids and that this is consistent with a mode of action involving the sequencing of microtubule-associated proteins (MAPs) by nonspecific electrostatic interactions. The inhibitory potency of phosphatidylinositol (PI) is, however, considerably larger than predicted by this model. The effects of PI on MAP2/tubulin microtubule assembly have therefore been examined in greater detail by preparing phosphatidylcholine (PC) liposomes doped with increasing amounts of PI. We show that when the PI is sufficiently dispersed by dilution with PC, it inhibits microtubule assembly by binding to MAP2 with an apparent stoichiometry, after correction for the bilamellar nature of the liposomes, of 1:1 mol.mol-1 PI:MAP2. Furthermore, we show that the Kd of this interaction is in the submicromolar range. 相似文献
5.
A large series of mouse monoclonal antibodies was found to inhibit the proliferation of T-cell growth factor (TCGF)-dependent human T-cell blasts as measured by the incorporation of tritiated thymidine. The specificity of the antibody appeared to be irrelevant for inhibition and two T-cell-specific antibodies did not prevent the absorption of TCGF by treated T cells. It is suggested that the antibodies function by the indirect release of suppressor factors by Fc receptor-bearing TCGF-dependent cells. 相似文献
6.
Porins are pore-forming outer-membrane proteins which serve as a non-specific pathway for the entry of hydrophilic molecules into Gram-negative bacteria. We studied four strains of Haemophilus influenzae that had decreased permeability to chloramphenicol associated with diminished quantities of a 40 kDa major outer-membrane protein. Isogenic pairs of organisms containing and lacking this protein were compared. The latter strains grew more slowly and were less permeable to sucrose and raffinose. They were also more resistant to multiple hydrophilic antibiotics than an isogenic strain containing the 40 kDa protein and were less permeable to penicillin G and chloramphenicol. We conclude that the 40 kDa outer-membrane protein functions as a porin in H. influenzae. 相似文献
7.
Influence of neighbouring base sequence on N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis in the lacI gene of Escherichia coli 总被引:10,自引:0,他引:10
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forward mutations within the first 540 base-pairs of the lacI gene of Escherichia coli were cloned and sequenced. In total, 167 MNNG-induced independent mutations were characterized, with G.C to A.T transitions accounting for all but three of the mutations. This mutagenic specificity is consistent with the mispairing predicted by the methylation of the O6 position of guanine. The characterization of such large numbers of mutations permitted an analysis of the influence of local DNA sequence on mutagenesis. This analysis revealed a strong influence by the 5' flanking base. On average, guanine residues preceded (5') by a guanine or an adenine residue were, respectively, nine times and five times more likely to mutate after treatment with MNNG than those preceded by a pyrimidine residue. 相似文献
8.
The small intestine of the rat was shielded during total-body irradiation (TBI) to evaluate the effects of radiation dose and length of intestine shielded on survival. Sprague-Dawley rats were anesthetized in groups of 10. Using aseptic surgical procedures 80, 40, 20, or 10 cm, or none of the proximal or distal small intestine were temporarily exteriorized and shielded during irradiation with photons from an 18 MeV linear accelerator. Less than 17% of the dose was delivered to the shielded intestines. In unshielded animals deaths occurred from Days 4 to 6 with 13, 15, or 17 Gy and from Days 8 to 30 with 9, 11, and 12 Gy. However, in all animals exposed to 15 Gy with all or part of the small intestine shielded, survival was increased to between 5 and 9 days. Shielding of the distal small intestine was more effective in prolonging survival than shielding of the proximal small intestine. The previously identified target of radiation damage in the small intestine is the crypt stem cell. In this study, the analysis of histological specimens of shielded and irradiated small intestine suggested that humoral factors also influence intestinal histology and survival after irradiation. These humoral factors are thought to originate from the irradiated body tissues, the shielded proximal intestine, and the shielded distal intestine. Further studies are required to identify these factors and to determine their mode of action and their therapeutic potential after radiation damage to the small intestine. 相似文献
9.
R G Burns 《Cell motility and the cytoskeleton》1990,17(3):167-173
The concentration of estramustine phosphate required to inhibit the assembly or to induce the disassembly of chick brain MAP2:tubulin microtubules is markedly dependent upon the microtubule protein concentration. Analysis of this relationship shows that estramustine phosphate and tubulin compete for common MAP2 sites, that MAP2 can bind 5-6 moles.mole-1 estramustine phosphate, and that the Kd of these sites is congruent to 20 microM estramustine phosphate. It is proposed that two molecules of estramustine phosphate interact with each of the three tubulin-binding sites of MAP2 and inhibit the MAP2:tubulin interaction by neutralising two highly conserved basic residues. 相似文献
10.
Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein 总被引:7,自引:0,他引:7
A J Gordon P A Burns D F Fix F Yatagai F L Allen M J Horsfall J A Halliday J Gray C Bernelot-Moens B W Glickman 《Journal of molecular biology》1988,200(2):239-251
The lac repressor has been studied extensively but a precise three-dimensional structure remains unknown. Studies using mutational data can complement other information and provide insight into protein structure. We have been using the lacI gene-repressor protein system to study the mutational specificity of spontaneous and induced mutation. The sequencing of over 6000 lacI- mutations has revealed 193 missense mutations generating 189 amino acid replacements at 102 different sites within the lac repressor. Replacement sites are not distributed evenly throughout the protein, but are clustered in defined regions. Almost 40% of all sites and over one-half of all substitutions found occur within the amino-terminal 59 amino acid residues, which constitute the DNA-binding domain. The core domain (residues 60 to 360) is less sensitive to amino acid replacement. Here, substitution is found in regions involved in subunit aggregation and at sites surrounding residues that are implicated in sugar-binding. The distribution and nature of missense mutational sites directs attention to particular amino acid residues and residue stretches. 相似文献