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Cyclin-dependent kinase inhibitor p21Waf1 is known to have alternative functions associated with positive regulation of proliferation, actin cytoskeleton remodeling and suppression of apoptosis. The goal of the present study was to assess the role of p21Waf1 in the establishment of the transformed phenotype of mouse embryo fibroblasts with stable expression of E1Aad5 and c-Ha-ras complementary oncogenes. Herein, we demonstrate that E1A/c-Ha-Ras-transformed p21Waf1-null fibroblasts possess some characteristic features of transformed cells, such as loss of contact inhibition, high saturation density, shortened cell cycle, inability to undergo cell-cycle arrest after DNA damage and serum deprivation, but, at the same time, they are not completely transformed in that they are unable to proliferate at clonal density, are anchorage-dependent, retain a fibroblast-like morphology with pronounced actin cytoskeleton and show reduced migration and invasion. Our data support the concept of p21Waf1 “tumor suppressor” having alternative oncogenic functions in the cytoplasm and for the first time indicate that p21Waf1 can be indispensable for complete oncogenic transformation. 相似文献
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M E Pospelov E V Ivanova G Ia Fra?kin 《Nauchnye doklady vysshe? shkoly. Biologicheskie nauki》1984,(1):35-37
The relative contribution of respiration photoinhibition and DNA damage in the lethal effect induced by 313 nm ultraviolet light (UV) has been investigated in some strains of the yeast Saccharomyces cerevisiae. It has been shown that cells inactivation is essentially due to photo-induced damage to DNA. By photoreactivation experiments it has been found that dimers of the pyrimidine bases are the main lethal photoproducts induced in the DNA by 313 nm ultraviolet light. 相似文献
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A structure of potentially active and inactive genes of chicken erythrocyte chromatin upon decondensation. 总被引:1,自引:1,他引:1 下载免费PDF全文
In the presence of 3 mM MgCl2 DNase I cleavage of bulk, globin and ovalbumin gene chromatin in chicken erythrocyte nuclei generates fragments which are multiples of a double-nucleosome repeat. However, in addition to the dinucleosomal periodicity beta-globin gene chromatin was fragmented into multiples of a 100 b.p. interval which is characteristic for partially unfolded chromatin. This distinction correlates with higher sensitivity of beta-globin domain to DNase I and DNase II as compared to the inactive ovalbumin gene. At 0.7 mM MgCl2 where these DNases fragment bulk chromatin into series of fragments with a 100 b.p. interval, the difference in digestibility of the investigated genes is dramatically decreased. When chromatin has been decondensed by incubation of nuclei in 10 mM Tris-buffer, DNase II generates a typical nucleosomal repeat, and the differential nuclease sensitivity of the analyzed genes is not observed. The data suggest that higher nuclease sensitivity of potentially active genes is due to irregularities in higher order chromatin structure. 相似文献
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Electrophoretic properties of chromatin subunits--nucleosomes--obtained by treatment of chromatin with the Serratia marcescens endonuclease have been studied. Double-stranded breaks of DNA between adjacent nucleosomes do not necessarily lead to their disjunction. Fragmentation of the DNA within the nucleosomes may proceed simultaneously with the breakdown of the DNA between the nucleosomes at early stages of the endonuclease digestion. Electrophoretic mobility and chromatographic properties of mononucleosomes, their dimers and trimers with internally degraded DNA was not changed. It has been deduced that the integrity of chromatin particles with internally fragmented DNA is supported by histone interaction inside and between the nucleosomes. 相似文献
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M.V. Abramova E.A. Zatulovskiy S.B. Svetlikova V.A. Pospelov 《The international journal of biochemistry & cell biology》2010,42(11):1847-1855
HDAC inhibitors (HDACIs) are capable of suppressing the cell growth of tumour cells due to the induction of apoptosis and/or cell cycle arrest. This allows of considering HDACIs as promising agents for tumour therapy. The final outcome – apoptotic cell death or cell cycle arrest – depends on the type of tumour and cellular context. In this report, we addressed the issue by analysing effects produced in E1A + Ras-transformed MEF cells by HDAC inhibitors sodium butyrate (NaB), Trichostatin A (TSA) and some others. It has been shown that the HDACIs induced cell cycle arrest in E1A + Ras-transformed cells but not apoptosis. The antiapoptotic effect of HDACIs is likely to be a result of NF-κB-dependent signaling pathway activation. HDACI-induced activation of NF-κB takes place in spite of a deregulated PI3K/Akt pathway in E1A + Ras cells, suggesting an alternative mechanism for the activation of NF-κB based on acetylation. HDACI-dependent activation of NF-κB prevents the induction of apoptosis by cytostatic agent adriamycin and serum deprivation. Accordingly, suppression of NF-κB activity in HDACI-arrested cells by the chemical inhibitor CAPE or RelA-siRNA resulted in the induction of an apoptotic programme. Thus, our findings suggest that the activation of the NF-κB pathway in HDACI-treated E1A + Ras-transformed cells blocks apoptosis and may thereby play a role in triggering the programme of cell cycle arrest and cellular senescence. 相似文献
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