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41.
Dual Cyclin-Binding Domains Are Required for p107 To Function as a Kinase Inhibitor 总被引:11,自引:6,他引:5
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Enrique Castao Yelena Kleyner Brian David Dynlacht 《Molecular and cellular biology》1998,18(9):5380-5391
The retinoblastoma (pRB) family of proteins includes three proteins known to suppress growth of mammalian cells. Previously we had found that growth suppression by two of these proteins, p107 and p130, could result from the inhibition of associated cyclin-dependent kinases (cdks). One important unresolved issue, however, is the mechanism through which inhibition occurs. Here we present in vivo and in vitro evidence to suggest that p107 is a bona fide inhibitor of both cyclin A-cdk2 and cyclin E-cdk2 that exhibits an inhibitory constant (Ki) comparable to that of the cdk inhibitor p21/WAF1. In contrast, pRB is unable to inhibit cdks. Further reminiscent of p21, a second cyclin-binding site was mapped to the amino-terminal portions of p107 and p130. This amino-terminal domain is capable of inhibiting cyclin-cdk2 complexes, although it is not a potent substrate for these kinases. In contrast, a carboxy-terminal fragment of p107 that contains the previously identified cyclin-binding domain serves as an excellent kinase substrate although it is unable to inhibit either kinase. Clustered point mutations suggest that the amino-terminal domain is functionally important for cyclin binding and growth suppression. Moreover, peptides spanning the cyclin-binding region are capable of interfering with p107 binding to cyclin-cdk2 complexes and kinase inhibition. Our ability to distinguish between p107 and p130 as inhibitors rather than simple substrates suggests that these proteins may represent true inhibitors of cdks. 相似文献
42.
M. Filek J. Biesaga-Kościelniak I. Marcińska M. Cvikrová I. Macháčková J. Krekule 《Biologia Plantarum》2010,54(3):483-487
The contents of endogenous free and conjugated polyamines, putrescine (Put) and spermidine (Spd), were determined during 9
week of vernalization (at 5 °C) in winter wheat seedlings cultivated on Murashige and Skoog media without (MS0) and with 2
mg dm−3 zearalenone (MSZEN). At the 4th week of chilling treatment, which is sufficient to induce generative development in 30 % of plants, the marked increase in
free and conjugated forms of Put and free Spd were observed. The presence of ZEN in medium significantly accelerated the vernalization.
About 20 % of plants treated with ZEN flowered already after 2 weeks and 40 % after 3 weeks of chilling. Significantly higher
content of free Put was determined in roots grown on MSZEN compared with MS0 during the first 5 weeks of vernalization with
maximum at the 4th week. After germination, a marked decrease in free Spd content was observed both in plants grown on MS0 and MSZEN. Application
of ZEN significantly slowed down the Spd decline in leaves and roots during the first and second week of vernalization. The
content of Spd and its conjugates decreased in vernalized plants after 1 week of cultivation at 20 °C. 相似文献
43.
F Krizsa Z Borbényi E Arokszállásy I Cserháti 《Folia haematologica (Leipzig, Germany : 1928)》1980,107(4):683-687
The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms. 相似文献
44.
45.
Changes in the duration and size of the vulnerable period of the myocardium in the presence of respiratory changes were studied in acute experiments on rats. The limits of the vulnerable period were determined by directly stimulating the heart during ventilation via the enlarged respiratory dead space, during hyperventilation and during heart failure. In the control group (normal ventilation without enlargement of the dead space), the vulnerable period lasted 5.7 +/- 0.76 ms. During ventilation via the enlarged dead space, hypercapnic hypoxaemia developed and the vulnerable period was markedly prolonged (18.55 +/- 5.29 ms) by a shift of its inner limit to the left. Hyperventilation caused normoxic to hyperoxic hypocapnia and markedly reduced the duration of the vulnerable period (8.17 +/- 2.21 and 9.31 +/- 2.38 ms respectively). The vulnerable period lengthened the most in heart failure (25.46 +/- 3.93), mainly as a result of a shift of its outer limit. In all the experimental groups there was a shift of the vulnerable period to the right, which was fastest in hypercapnic hypoxaemia and slowest in hyperoxic hypocapnia. The administration of Inderal (3 mg/kg i.p.) or Arfonad (50 mg/kg i.p.) markedly shortened the vulnerable period during hypercapnic hypoxaemia (9.87 +/- 2.78 and 9.32 +/- 2.16 ms respectively), but did not block the shift. Lengthening of the vulnerable period during hypercapnic hypoxaemia was probably due to activation of sympathetic nerves via beta-adrenergic receptors. 相似文献
46.
The production of L-lysine fromDL-α-amino-ε-caprolactam (DL-ACL) by new strains producingL-α-amino-ε-caprolactamase and aminocaprolactam racemase is described. Optimal conditions for hydrolysis ofL-ACL byCryptococcus sp. and for racemization of ACL by cells of a strain isolated in nature and identified asPseudomonas sp. were determined. Synthesis ofL-α-amino-ε-caprolactamase is induced byDL-ACL orL-lysine with the same effectivity. A positive effect of phosphates (potassium salts) on reduction of the induction lag was
detected, the synthesis of this enzyme was found to be repressed by glucose and some possibilities of the reversion of this
repressive effect were demonstrated. Under conditions optimal for the production of both enzymes a quantitative theoretical
conversion of 10 % aqueousDL-ACL toL-lysine by a mixture of native cells in a mass ratio of 1: 2 (producer of ACL-hydrolase to producer of ACL-racemase) occurred
in 8 h at 40 °C and pH 8.0 相似文献
47.
48.
Summary A male fetus of a pregnancy known to be at risk for X-linked mental retardation with fragile site Xq27 was found to be affected by demonstrating the marker X-chromosome in five of 180 (2.8%) of metaphases derived from amniocytes cultured in medium 199. The results were confirmed in fetal lymphocytes (25 of 86 metaphases, i.e. 29%), and fetal fibroblasts (five of 100 metaphases when cultured in medium 199, and 14 of 100 after exposure to methotrexate for 43 h).This work was supported in part by a research grant from the Deutsche Forschungsgemeinschaft 相似文献
49.
A González-Fernández J Sans P Aller C de la Torre 《Cell biology international reports》1985,9(3):237-243
Bromosubstitution for most of the S period in synchronous populations of Allium cepa L. meristematic cells resulted in a delay in the late S-G2 transition point where protein synthesis is needed for later mitotic entrance to occur. This retardation in the position of the transition point was not accompanied by the expected delay in the entrance into mitosis, suggesting that such protein synthesis is a requisite, but not a timer for prophase triggering. 相似文献
50.
F García J Sánchez J Planas 《Comparative biochemistry and physiology. A, Comparative physiology》1987,87(4):947-950
1. Male quails submitted 20 and 120 days to a low iron diet (7 ppm) were compared to female laying quails, exposed for 30 days to the same low iron regime, in order to compare the response of the iron metabolic control under a single (erythropoiesis) or a doubled (erythropoiesis and egg formation) iron demand. 2. Iron deposit in storage organs, the classical hematology and the intestinal iron absorption were analyzed in these animals. 3. In males, after 120 days, the iron deposits were reduced 50 and 75%, but hematological values (hematocrit and hemoglobin concentration) were normal, although in laying quails, after 30 days, an anemic condition was evident in both blood parameters and iron deposits, provoking an iron deficient erythropoiesis. 4. The enhancement of the intestinal iron uptake, confirms the anemic character of these birds. 相似文献